News

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.

Re-emergence of Human Enterovirus D68 (EV-D68)

Written by: Sunil K. Sood, MD

Enteroviruses (EV) circulate year-round, but illnesses caused by these viruses peak in the summer and autumn months in the U.S. Common clinical manifestations include mild gastroenteritis, meningitis, non-specific illness with or without rash, and hand-foot-mouth disease. Common reasons for pediatric admissions are fever in an infant, and meningitis. EV-D68, however, manifests primarily as a respiratory illness. In late August of this year, there was an unusual spike in Emergency Department visits for severe respiratory illness, which correlated with increased detection of rhinovirus/enterovirus, at the Children's Mercy Hospital in Kansas City, Missouri. Over a 3- 4 week period, there were 475 admissions including about a 100 to their PICU and an excess of 100 emergency room or urgent care visits per day. (Mary Anne Jackson, MD personal communication to Lorry Rubin, MD; and Angela Myers, MD personal communication. Shortly thereafter, a similar cluster was observed at the University of Chicago Comer Children's Hospital. An investigation by the CDC revealed that 80-95% of nasopharyngeal swab specimens tested yielded EV-D68 RNA. The age range was 6 weeks to 16 years. As of September 30, 2014, 43 states have reported EV-D68 related illnesses. http://www.cdc.gov/non-polio-enterovirus/about/EV-D68.html. The last known clusters of EV-D68 associated with respiratory illness in the United States during were reported during 2009 and 2010. (CDC. Clusters of acute respiratory illness associated with human enterovirus 68—Asia, Europe, and United States, 2008–2010. MMWR 2011;60:1301–4.)

EV, encompassing Polioviruses, Coxsackie A and B, Echo and other (numbered) viruses, belong to the Picornavirus Family, which include rhinoviruses. Rhinoviruses are among the most common pathogens of humans, and are a well known cause of upper and lower respiratory tract infection. Most currently used respiratory viral assay panels detect RNA that is generic for EV and rhinoviruses, and are reported as "rhinovirus/enterovirus." Because "rhinovirus/enterovirus" is reported year round, and most such children do not have severe illness, the current outbreak represents an emerging infection, and warrants further study of its epidemiology. At the time of this writing, the time course and extent of the outbreak cannot be predicted.

Current guidance from the CDC is to "consider EV-D68 as a possible cause of acute, unexplained severe respiratory illness, even if the patient does not have fever." http://www.cdc.gov/non-polio-enterovirus/about/EV-D68.html It is important to recognize the following unusual clinical characteristics among the children studied thus far:

  • The majority have presented without fever
  • Wheezing is prominent and hypoxemia is common
  • The presentation is more severe in children with known reactive airways disease
  • ICU admit rate is high; some have required mechanical ventilation or ECMO

A new dimension to this outbreak is the re-emergence of acute neurologic illness with focal limb weakness, first observed in California last year. Nine cases were identified during August 9–September 17, 2014 in Colorado.This neurologic illness appears to follow the respiratory illness by about 2 weeks. MRI findings can include a spinal cord lesion largely restricted to gray matter. Acute onset of focal limb weakness in a child occurring on or after August 1, 2014, should be reported immediately to local health departments.

Treatment is supportive, and until there is future understanding of the epidemiology, it is prudent to maintain suspected inpatients on contact and droplet precautions for the duration of illness.

References:

Severe Respiratory Illness Associated with Enterovirus D68 — Missouri and Illinois, 2014Weekly September 12, 2014 / 63(36);798-799 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6336a4.htm?s_cid=mm6336a4_w 

CDC. Clusters of acute respiratory illness associated with human enterovirus 68—Asia, Europe, and United States, 2008–2010. MMWR 2011;60:1301–4.CDC. Clusters of acute respiratory illness associated with human enterovirus 68—Asia, Europe, and United States, 2008–2010. MMWR 2011;60:1301–4. 

http://www.cdc.gov/non-polio-enterovirus/about/EV-D68.html 

Ebola Outbreak - What can you do?

Organizations and agencies involved in fighting the continuing West Africa Ebola crisis are calling for medical personnel, supplies and training to address the outbreak and its impact on health systems in one of the poorest areas in the world. The links below give information on opportunities to volunteer, donate, and learn more about the outbreak and needs:

Volunteer:
Médecins Sans Frontières (Doctors Without Borders) is seeking physicians and nurses with experience in highly contagious wards and personal protective equipment, who are familiar with infection control and safety practices inside isolation areas, and are available for 6-8 weeks for a field assignment in West Africa. Information on MSF's work in West Africa is here.

The United States Agency for International has created a registry for experienced health sector workers interested in volunteering to help those affected by the outbreak. The agency may share information submitted with nongovernmental organizations working in West Africa or with the Centers for Disease Control and Prevention.

The Centers for Disease Control and Prevention has developed a safety training course for healthcare workers who plan to go to West Africa to treat patients in Ebola units. The three-day courses will be taught by CDC staff epidemiologists, infection preventionists, MSF staff members and other professionals. Ten course sessions are scheduled from Oct. 6 to January 4, 2015. Detailed information is available here.

Donate:
The CDC Foundation is helping staff deployed by the Centers for Disease Control and Prevention meet needs that currently include laptop computers for communication and disease tracking, personal protective equipment, thermal scanners, infection control training, as well as isolation beds through its Global Disaster Response Fund.

The Global Giving Ebola Epidemic Relief Fund has established a fund to provide aid organizations on the ground in West Africa with resources that include medical supplies, protective equipment and educational campaigns.

Partners in Health is seeking donations to support its work with local organizations in Sierra Leone and Liberia to set up Ebola treatment units in rural locations, train health care workers to identify and treat patients and strengthen primary health care.

Learn more:
IDSA News: The September edition provides a compilation of informational links, including to the IDSA Ebola Guidance for ID Clinicians, CDC Ebola evaluation guidelines, resources, and information for volunteers, SHEA Ebola resources, and journal articles on Ebola.

Vaccines - Calling The Shots - PBS Special

Measles, mumps, whooping cough. Diseases that were largely eradicated a generation ago in the United States are returning. Why?

Read more: Vaccines - Calling The Shots - PBS Special

How Next Generation Sequencing is Changing Pediatric Infectious Diseases

Written by: Pia S. Pannaraj, MD, MPH

The technical advancement in microbial genomics is revolutionizing the field of infectious diseases.  The first complete genome sequence of a free-living organism, Haemophilus influenzae, was completed in 1995.  Since then, over 23,000 bacteria, 600 fungi and 4000 viruses have been sequenced. Most were completed in the last year and many more are in progress thanks to new high-throughput DNA sequencing technologies, a.k.a. Next Generation Sequencing (NGS).

Why is this exciting for pediatric infectious disease specialists?

NGS allows us to look at the complete DNA fingerprint of microbes with increasing speed and decreasing cost. We have deepened our ability to investigate outbreaks, detect antibiotic resistance genes, characterize difficult-to-culture organisms, and monitor host-microbe interactions at an unprecedented level of detail.

For example, the Centers for Disease Control and Prevention (CDC)'s PulseNet uses NGS to quickly detect multi-state foodborne outbreaks caused by Listeria, Escherichia coli, Salmonella and other dangerous bacteria. Bacterial cultures may take up to 3 days to grow in a laboratory while the foodborne pathogen continues to spread. NGS can determine information about the species, serovar, and subtype of bacteria within hours. This technology was used to determine the origin of a recent multi-state outbreak of Listeria in Hispanic-style cheese products. In March 2014, the Food and Drug Administration (FDA) suspended food production by Roos Food, Inc. after their cheese tested positive for a strain of Listeria indistinguishable from the outbreak strain. A 2011 multi-country outbreak of Shiga toxin-producing E. coli O104:H4 affected 4075 people, including 908 cases of hemolytic-uremic syndrome and 50 deaths. Researchers analyzed and published the complete genome mapping of the outbreak strain within 3 months of the outbreak's inception. A horizontal genetic transfer of a Shiga-toxin-encoding phage from an enterohemorrhagic E. coli onto an enteroaggregative E. coli strain resulted in an accumulation of synergistic virulence factors. Data sharing and open collaboration allowed researchers across the globe to analyze the outbreak strain with extraordinary speed.

Virulent pathogens – new and old – and increasingly multidrug resistant pathogens are becoming greater infection control challenges. In 2011, an outbreak of carbapenem-resistant Klebsiella pneumoniae affected 18 patients at the U.S. National Institutes of Health Clinical Center, 11 of whom died, despite early implementation of infection control procedures. Whole genome sequencing performed on patient and environmental isolates lead to the discovery that the index patient had left the hospital 3 weeks before the strain was isolated from another patient indicating that K. pneumoniae could silently colonize patients. Thus, effective surveillance protocols before isolation of multi-drug resistant strains were as important as infection control strategies after isolation.

The aggressive and highly lethal Ebola virus is an example of a pathogen that has been hard to study due difficulties in obtaining samples from remote areas where the outbreaks have occurred. Researchers are rapidly studying the current outbreak strain of the Ebola virus sequence to obtain insights on its origin, understand the virus' mutation over time, learn about the mechanisms underlying its pathogenicity, and determine how to design more sensitive and accurate diagnostic tests in the field. The current outbreak so far has caused 2,127 cases of disease and 1,145 deaths in Guinea, Liberia, Nigeria, and Sierra Leone.

Finally, sequencing technology has transformed our thinking about microbes on and in the human body. The human body contains over 100 trillion bacteria cells. We have just recently come to appreciate how these symbiotic microbes benefit us by breaking down our food, suppressing pathogenic bacteria, and nurturing our immune system. Multiple studies have revealed an intriguing association between the types and diversity of microbes in a child's gut and risk of asthma, diabetes, obesity, response to vaccines, and even behavior. Prospective studies in germ-free mice support these findings. What is important for pediatricians to know is that early exposures determine an infant's microbial composition as an infant. Mode of delivery, gestational age, breastfeeding vs. formula feeding, administration of antibiotics and the local environment all play a role in obtaining the "right" microbes. How do we know which are the "right" microbes? There is much more to discover, and NGS technology has opened the door to explore this question and many more.

The 5th Annual International Pediatric Antimicrobial Stewardship Conference

An Attendee's Perspective (and why all of you should go)
Written by: Saul Hymes, MD

Every year so many large conferences, courses, and annual meetings vie for our attention and our dollars.

Read more: The 5th Annual International Pediatric Antimicrobial Stewardship Conference

Does the Availability of Testing Improve Clinical Care?

Written by: Pui-Ying Iroh Tam, MD

Health outcomes for Americans have improved substantially over the last generation due to a number of factors including improved sanitation, vaccinations, increased education, and better health care.

Read more: Does the Availability of Testing Improve Clinical Care?

International Travel and Acquisition of Multidrug Resistant Organisms

Written by: Christina Gagliardo, MD

As pediatric infectious disease physicians, there are several key questions we all ask in order to obtain a thorough exposure history, including: "Do you have pets or animal exposures? Are your vaccines up to date? Have you ever travelled outside the country?" This last question has become increasingly important for several reasons which include ascertaining risk for tropical infections such as tuberculosis, malaria, typhoid, or dengue, vaccine-preventable illnesses such as polio and measles, but also to assess risk for colonization with multidrug resistant bacteria. A growing number of studies demonstrate acquisition of multidrug resistant bacteria during travel abroad. Likely every pediatric infectious disease physician has encountered an otherwise healthy child who is either colonized with, or has an infection from an extended spectrum beta-lactamase (ESBL) producing or other multidrug resistant organism (MDRO) with no discernible classic risk factors such as prior hospitalization, prior antibiotic use, or other medical problems. An underappreciated and likely relevant part of the history for MDRO colonization is international travel.

Travel to Southeast Asia appears to be an emerging risk factor for acquisition of ESBL-producing Enterobacteriaceae with several prospective cohort studies identifying international travel as a risk factor for colonization and travel to India or the Indian subcontinent as the highest risk factor (1-5).
A prospective study of 100 Swedish adults travelling outside Northern Europe demonstrated 24 individuals with negative pre-travel stool samples were colonized with ESBL-producing Escherichia coli after return home. They found a statistically significant higher risk of acquisition of ESBL-producing Escherichia coli with travel to India and an association with gastroenteritis related to travel, which could be a surrogate parameter for exposure to fecally contaminated food or water (2).

Van der Bij provides a comprehensive list of studies which demonstrate the role international travelers play in the global spread of MDROs, some of whom did report contact with healthcare systems abroad (6). Several large clinical trials are currently looking at the acquisition of MDR Enterobacteriaceae including COMBAT: Carriage of Multidrug Resistant Bacteria After Travel (ClinicalTrials.gov Identifier: NCT01676974) and the VOYAG-R Study: Acquisition of Multidrug-resistant Bacteria After Travel in the Tropics: Prevalence, Determinants and Length of Carriage (ClinicalTrials.gov Identifier: NCT01526187). These studies are also evaluating duration of colonization and rate of secondary transmission within households. VOYAG-R reported on three healthy French travelers returning from India who reported no contact with any healthcare center while abroad who acquired carbapenemase-producing Enterobacteriaceae (CPE) (7).

A recent study utilized a metagenomic approach and investigated resistance genes in the human gut microbiota after international travel. They reported high rates of acquisition of the ESBL- encoding gene blaCTX-M and quinolone resistance encoding genes qnrB and qnrS related to international travel. The prevalence of the resistance genes increased from 9.0%, 6.6%, and 8.2% before travel to 33.6%, 36.9%, and 55.7% after travel, respectively (5).

These findings raise several questions and have implications for policies regarding infection control measures. Should we counsel patients about these risks during pre-travel consultation when there is no specific intervention or recommendation to be made? Should we screen and isolate patients after travel abroad if they are hospitalized? In France the Healthcare Safety Advisory Committee made national recommendations to screen and place any individual transferred from or hospitalized outside France on contact isolation (6). While at this time there is certainly not enough evidence to support screening and isolating every person who has recently travelled, the impact of international travel on the spread of MDROs is crucial to understand on the patient and public health level to determine optimal interventions and policies.

References:

  1. Kennedy K, Collignon P. Colonisation with Escherichia coli resistant to "critically important" antibiotics: a high risk for international travelers. Eur J Clin Microbiol Infect Dis. 2010;29:1501–6
     
  2. Tängdén T, Cars O, Melhus A, Lowdin E. Foreign travel is a major risk factor for colonization with Escherichia coli producing CTX-M–type extended-spectrum beta-lactamases: a prospective study with Swedish volunteers. Antimicrob Agents Chemother. 2010;54:3564–8
     
  3. Ostholm-Balkhed A, Tarnberg M, Nilsson M, Nilsson LE, Hanberger H, Hallgren A, et al. Travel-associated faecal colonization with ESBL-producing enterobacteriaceae: Incidence and risk factors. J Antimicrob Chemother. 2013;68:2144–53
     
  4. Paltansing S, Vlot JA, Kraakman MEM, Mesman R, Bruijning ML, Bernards AT, et al.Extended-spectrum β-lactamase–producing enterobacteriaceae among travelers from the Netherlands. Emerg Infect Dis. 2013;19:1206–13
     
  5. von Wintersdorff CJH, Penders J, Stobberingh EE, Oude Lashof AML, Hoebe CJPA, Savelkoul PHM et al. High acquisition rates of antimicrobial drug resistance genes after international travel, the Netherlands. Emerg Infect Dis. 2014
     
  6. van der Bij, AK, Pitout JDD. The role of international travel in the worldwide spread of multiresistant Enterobacteriaceae. J. Antimicrob. Chemother. (2012)67 (9): 2090-2100
     
  7. Ruppé E, Armand-Lefèvre L, Estellat C, El-Mniai A, Boussadia Y, Consigny PH, Girard PM, Vittecoq D, Bouchaud O, Pialoux G, Esposito-Farèse M, Coignard B, Lucet JC, Andremont A, Matheron S. Acquisition of carbapenemase-producing Enterobacteriaceae by healthy travellers to India, France, February 2012 to March 2013 . Euro Surveill. 2014;19 (14)

JPIDS Article Review: A National Study of the Impact of Rapid Influenza Testing on Clinical Care in the Emergency Department

Written by: Sunil K. Sood, MD

Read more: JPIDS Article Review: A National Study of the Impact of Rapid Influenza Testing on Clinical Care...

Preserving the Future of Pediatric Infectious Diseases

Written by: Matthew Kronman, MD, MSCE

In the last cycle of the match for fellowship positions in Pediatric Infectious Diseases, there were approximately 80% as many applicants (55 total) as there were available fellowship positions [1].

Read more: Preserving the Future of Pediatric Infectious Diseases

JPIDS Article Review: The Safety and Immunogenicity of Rotavirus Vaccination in Infants with Intestinal Failure

Written by: Rebecca Wallihan, MD 

Read more: JPIDS Article Review: The Safety and Immunogenicity of Rotavirus Vaccination in Infants with...

MERS Update: Key Points – Middle East Respiratory Syndrome Coronavirus (MERS-CoV)- 5/12/2014

CDC has provided updated key points regarding the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), dated 5/12/2014. Updates include information about the second imported case of MERS in the United States.

Read more: MERS Update: Key Points – Middle East Respiratory Syndrome Coronavirus (MERS-CoV)- 5/12/2014

CDC announces second imported case of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection in the United States

CDC and Florida Department of Health officials are investigating the second case of MERS-CoV infection in the United States. MERS-CoV, a virus relatively new to humans, was first reported in Saudi Arabia in 2012.  On May 2, 2014 CDC reported the first case of MERS in the United States.

WHO:

  • Tom Frieden, M.D., M.P.H., Director, U.S. Centers for Disease Control and Prevention
     
  • Anne Schuchat, M.D. (RADM, USPHS) Assistant Surgeon General, United States Public Health Service; Director, National Center for Immunization and Respiratory Diseases
     
  • John H. Armstrong, MD, FACS, FCCP Florida's State Surgeon General and Secretary of Health

WHEN: Monday, May 12, 2014 at 2:00 p.m. ET

DIAL-IN:
Listen-only: 877-546-1574
Passcode: CDC MEDIA

Transcript:
A transcript of this media availability will be available following the briefing at the CDC web site at www.cdc.gov/media.

U.S. Department of Health and Human Services
CDC works 24/7 saving lives, protecting people from health threats, and saving money through prevention. Whether these threats are global or domestic, chronic or acute, curable or preventable, natural disaster or deliberate attack, CDC is the nation's health protection agency.

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