Written by: Rana F. Hamdy, MD, MPH

On March 3, 2016, St. Jude and PIDS hosted the 3rd annual St. Jude/PIDS Pediatric Transplant ID Symposium. This one-day symposium was held the day prior to the St. Jude/PIDS Research Conference and brought together leaders in the field of pediatric transplant ID for presentations and discussions on topics related to infections in children undergoing hematopoietic stem cell or solid organ transplantation.

Highlights from the meeting included:

  • Dr. Sandy Feng, Professor of Surgery from the University of California San Francisco began the symposium with an overview of the immune system, immunosuppressive therapeutic agents, and their mechanisms of action, followed by a discussion of the feasibility of immunosuppressive withdrawal in liver transplant recipients.
  • Dr. Steven Holland, Chief of the Laboratory of Clinical Infectious Diseases at the National Institutes of Health, discussed the status of hematopoietic stem cell transplantation as a treatment option for primary immunodeficiency syndromes with myeloid defects including chronic granulomatous disease, Job’s syndrome, and GATA2 deficiency.
  • Dr. Michael Ison, Medical Director of the Transplant & Immunocompromised Host Infectious Diseases Service at Northwestern University Feinberg School of Medicine, described the epidemiology of diarrhea in transplant recipients and discussed the optimal diagnostic approach to these patients.
  • Dr. Brian Fisher, Assistant Professor of Pediatrics at The Children’s Hospital of Philadelphia, presented results from a multicenter clinical research study of the epidemiology and outcomes of respiratory viral infections in HSCT and SOT patients. Dr. Fisher discussed the process of establishing the infrastructure for performing large multi-center clinical epidemiology research studies in pediatric transplant patients, highlighting the opportunities that collaboration via the St. Jude/PIDS Transplant ID Symposium affords, and he invited any interested individuals to join the Transplant Research Network to discuss future opportunities for collaboration.
  • Dr. Theoklis Zaoutis, Professor of Pediatrics and Epidemiology and Chief of the Division of Infectious Diseases at The Children’s Hospital of Philadelphia, reviewed the epidemiology of invasive fungal infections (IFIs) in immunocompromised children; the diagnosis of IFIs, including the role of biomarkers; the evidence for antifungal prophylaxis among HSCT recipients and children with leukemia; and optimal treatment strategies for immunocompromised children with IFIs.
  • Dr. Gregory Storch, Professor of Pediatrics and Molecular Microbiology from Washington University School of Medicine, discussed emerging trends in diagnostic microbiology and the application of new diagnostic testing methods in managing infections in pediatric transplant recipients.
  • Dr. Michael Green, Professor of Pediatrics at Children’s Hospital of Pittsburgh, discussed the role of the Organ Procurement Transplant Network/United Network for Organ Sharing in protecting solid organ transplant recipients from unanticipated donor-derived infections.
  • Dr. Lara Danziger-Isakov, Professor of Pediatrics at Cincinnati Children’s Hospital Medical Center, discussed the components of a pre-transplant evaluation for identifying and mitigating the risk of post-transplant infections.
  • Drs. Hayley Gans and Gabriela Maron presented the top six papers in transplant ID in 2015-2016.

Interspersed between the presentations were interactive breakout sessions built around case presentations, with lively discussions that provided an opportunity to explore variations in practice throughout the country.

A poster session also provided an opportunity to engage other symposium participants and learn about ongoing basic science, translational, and clinical research in pediatric transplant ID.

In total, 124 participants from 54 different institutions and 6 countries attended the St. Jude/PIDS Pediatric Transplant ID Symposium this year. Participants engaged with leaders in the field of pediatric transplant ID, discussed challenging cases and new research, and met colleagues from across the country, building new collaborations and networks. The next St. Jude/PIDS Pediatric Transplant ID Symposium will take place March 9, 2017 in Memphis, Tennessee.

Written by: Parvathi S Kumar MBBS, Andrés Alarcón MD

Since August 2015, a large outbreak of Lassa fever has devastated Nigeria, in West Africa. The index case of the current outbreak was reported from Bauchi in November, 2015.1 Secondary cases have been reported across 19 states in Nigeria. As of March of 2016, the Nigeria Center for Disease Control (NCDC) has reported a total of 254 cases (129 laboratory confirmed cases) and 137 deaths (suspected, probable and confirmed cases) with a case fatality rate (CFR) of 53.9%.2 The neighboring country of Benin detected an outbreak of Lassa fever on January 21st, 2016. Togo notified the World Health Organization (WHO) of its first 2 cases on March 9th 2016, and active surveillance of contacts are being monitored in Togo, Germany, and United States of America (USA). Currently, 2 secondary cases are being cared for in Germany and USA. The American citizen, a physician assistant is receiving care and treatment at Emory University Hospital in Georgia and is reportedly stable. The German patient who represents Europe's first case of locally acquired Lassa fever is being care for in Frankfurt, alongside four family members.

Typically, Lassa fever outbreaks have a low overall mortality rate of 1% with a mortality rate of 15-20% amongst hospitalized individuals.3,4 The unusually high CFR associated with the current outbreak is worrisome and remains unexplained. A heightened awareness resulting from the Ebola virus disease outbreak ravaging the area, coupled with the increasing capability to rapidly and accurately diagnose the condition may be contributing factors. Additionally, prior outbreaks may have been under reported when remote and rural areas of the country were primarily affected.

Lassa virus, an arenavirus, was first described in 1969, and named after the town in Nigeria where the first cases occurred.5 It is a zoonotic acute viral hemorrhagic illness lasting 1-4 weeks; endemic to West Africa, particularly Sierra Leone, Liberia, Guinea (Mano River region), and Nigeria. CDC estimates 100,000-300,000 Lassa virus infections in West Africa per year, with approximately 5,000 deaths.6 The neighboring countries of Benin, Togo, Ghana, and Mali report yearly outbreaks with peaks from December through February.7

The animal reservoir is a rodent of the genus Mastomys, commonly known as the “multimammate rat” that colonizes homes and peri-residential areas. The rodents once infected are typically asymptomatic; however, they can shed the virus in urine and droppings for a long time, possibly for the duration of its life time. Human infections result from direct contact with the rodent’s waste via inhalation or ingestion. Infection can also be acquired in the laboratory or through human to human transmission after exposure to the virus in the blood, tissue or secretions. Following an incubation period of 7-21 days, the infection results in severe hemorrhagic fever in 5-10% of the cases. Typically, the disease has a gradual onset, starting with fever, general weakness, and malaise. The symptoms are closely followed by pharyngitis, muscle pain, retrosternal chest pain, cough, bleeding from the mouth, nose, vagina or gastrointestinal tract, and the potential for associated hypotension and or sepsis.8 Recovery from a milder disease begins 8 to 10 days after disease onset with resolution of symptoms. Of importance, the disease is especially severe if acquired in the 3rd trimester of pregnancy resulting in more than 80% maternal mortality and fetal loss. Deafness secondary to sensorineural hearing (SNH) loss is a major morbidity associated with Lassa fever. It is estimated that SNH loss can occur in up to 25% of patients who survive the disease, making Lassa fever a major cause of deafness in endemic areas.8,9

Due to the increasing international travel and migration patterns, it is important to consider common and uncommon infectious etiologies of febrile illness in returning travelers to the USA or other non-endemic countries. In Lassa fever, ribavirin is most effective when given early in the disease and consideration should be made in consulting an infectious disease specialist to expedite potential compassionate use through the USA Food and Drug Administration (FDA) and Valeant Pharmaceuticals (Aliso Viejo, California). 10

If a case of Lassa fever is suspected, per CDC recommendations, it is prudent to immediately implement hospital infection-control policies, contact state and local health department for contact tracing, treatment recommendations, adherence to proper infection-control strategies, and proper diagnostic laboratory collection.12 Clinicians should notify local health authorities and CDC’s Viral Special Pathogens Branch immediately of any suspected cases of VHF occurring in patients residing in or requiring evacuation to the United States: 404-639-1115 or the CDC Emergency Operations Center at 770-488-7100 after hours.11


  1. Press Briefing on the Outbreak of Lassa fever in Nigeria by the Honourable Minister of Health. (Accessed March 25th 2016, at http://www.health.gov.ng/index.php/news-media/9-uncategorised/245-press-briefing-on-the-outbreak-of-lassa-fever-in-nigeria-by-the-honourable-minister-of-health.) 
  2. Lassa fever death rates in Nigeria higher than expected. (Accessed March 27th 2016, at http://www.cnn.com/2016/03/17/health/lassa-fever-outbreak-nigeria/.) 
  3. Ogbu O, Ajuluchukwu E, Uneke CJ. Lassa fever in West African sub-region: an overview. J Vector Borne Dis 2007;44:1-11.
  4. Centers for Disease C, Prevention. Imported Lassa fever--New Jersey, 2004. MMWR Morb Mortal Wkly Rep 2004;53:894-7.
  5. Frame JD, Baldwin JM, Jr., Gocke DJ, Troup JM. Lassa fever, a new virus disease of man from West Africa. I. Clinical description and pathological findings. Am J Trop Med Hyg 1970;19:670-6.
  6. Lassa fever. (Accessed March 25th 2016, at http://www.cdc.gov/vhf/lassa/.) 
  7. McCormick JB, King IJ, Webb PA, et al. A case-control study of the clinical diagnosis and course of Lassa fever. J Infect Dis 1987;155:445-55.
  8. Cummins D, McCormick JB, Bennett D, et al. Acute sensorineural deafness in Lassa fever. JAMA 1990;264:2093-6.
  9. McCormick JB, Webb PA, Krebs JW, Johnson KM, Smith ES. A prospective study of the epidemiology and ecology of Lassa fever. J Infect Dis 1987;155:437-44.
  10. Lassa Fever in Nigeria. (Accessed March 26th 2016, at http://wwwnc.cdc.gov/travel/notices/watch/lassa-fever-nigeria.) 
  11. Imported Lassa Fever --- New Jersey, 2004. (Accessed March 26th 2016, at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5338a2.htm.) 

Written by: Pranita D. Tamma, MD, MHS

Carbapenem-resistant Enterobacteriaceae (CRE) are just one of three microorganisms designated as having an “urgent” threat level by the United States Centers for Disease Control and Prevention (CDC). These microorganisms have an associated mortality upwards of 60% and are a danger to patients both in the United States and abroad. The prevalence of carbapenem-resistance among Klebsiella spp. causing healthcare-associated infections in US hospitals was 13% between 2009 and 2010, according to the CDC. The majority of US CRE isolates are from adult patients, but CRE infections appears to be a growing concern in children as well.

The term CRE refers to a heterogenous group of resistance mechanisms. The most common include either production of β-lactamases that hydrolyze the β-lactam ring of carbapenem antibiotics (i.e., carbapenemases) or production of extended-spectrum β-lactamases (ESBL) or AmpC β-lactamases in combination with a carbapenem-specific porin loss or mutation.

Carbapenemases are separated into three Ambler classes, distinguished by their structural homology. Class A and D carbapenemases require serine at their active site; while the Class B carbapenemases (i.e., the metallo-β-lactamases), require zinc at their active site. The most well-known members of Class A, B, and D are the KPC, NDM, and OXA carbapenemases, respectively.

CRE are defined as Enterobacteriaceae resistant to any carbapenem. Currently, most clinical microbiology laboratories do not distinguish carbapenemase-producing CRE from non-carbapenemase-producing CRE. Laboratories that do make this distinction usually use phenotypic methods (e.g., chromogenic assays, modified Hodge test, metallo-β-lactamases Etest, etc.) that are generally unable to identify the specific carbapenemase genes involved. Understanding whether CRE are carbapenemase-producing or non-carbapenemase producing has important infection control and antibiotic treatment implications. Carbapenemase-producing Enterobacteriaceae, unlike non-carbapenemase-producing CRE, are most often implicated in clinical outbreaks of CRE as these enzymes are generally harbored on mobile genetic elements (e.g., plasmids, transposons) and can spread easily from organism to organism, and often from patient to patient. With regards to antibiotic selection, some of the newer antibiotic agents in development, including the 2015 US Food and Drug Administration (FDA) approved ceftazidime-avibactam, seem to preferentially have activity against only specific carbapenemase classes.

There are two general treatment principles for the management of CRE infections. First, carbapenem resistance does not always translate to clinical failure upon subsequent treatment with carbapenem agents. Although the Clinical Laboratory Standards Institute breakpoint for meropenem, imipenem, and doripenem is 1 mcg/ml, pharmacokinetic-pharmacodynamic (PK-PD) studies indicate that carbapenems have activity against Enterobacteriaceae for MICs as high as 8-16 mcg/ml. Second, the mainstay of therapy is a combination of at least two agents. A number of observational studies have shown improved survival in patients who receive combination antibiotic therapy, preferably with at least one of the agents being a carbapenem.

It is the opinion of the author that appropriate therapy for an invasive CRE infection consists of either prolonged-infusion meropenem (or doripenem) for MICs of up to 8-16 mcg/ml OR ceftazidime-avibactam (if susceptible in vitro) in addition to a second agent such as an aminoglycoside or polymixin (colistin or polymixin B). Alternative options for second agents include tigecycline and fosfomycin. If meropenem or doripenem is not available, prolonged-infusion imipenem-cilastatin is a reasonable alternative, but limited stability of this agent at room temperature is a concern.

Ceftazidime-avibactam is generally active against Enterobacteriaceae (and Pseudomonas aeruginosa) producing Class A β-lactamases (ESBLs, KPCs), Class C β-lactamases (AmpC), and some Class D β-lactamases (OXAs). It is not active against those producing Class B carbapenemases. Phase 1 data of the pharmacokinetics, safety, and tolerability of a single dose of ceftazidime-avibactam in children as young as 3 months of age are available and Phase 2 studies evaluating ceftazidime-avibactam for children with complicated urinary tract infections and intra-abdominal infections are currently in progress.

Both colistin and polymixin B became clinically available before the establishment of contemporary drug-development procedures resulting in substantial gaps in knowledge of their PK-PD. For both agents, a loading dose is preferred. No head-to-head studies comparing the efficacy of these two agents are available. Colistin B is administered parenterally as an inactive prodrug colistin methanesulfonate (CMS), which is slowly and incompletely converted to colistin. Rapid and extensive renal clearance of CMS may reduce systemic availability of colistin. Because polymixin B does not have a prodrug and clinical data suggest reduced nephrotoxicity with this agent, many experts prefer polymixin B if both agents are available.

Tigecycline is a broad-spectrum, intravenous agent designed to be a poor substrate for tetracycline-specific efflux pumps. Its large volume of distribution results in low concentrations in blood, the epithelial lining fluid of the lungs, and the urinary tract. The FDA discourages the use of tigecycline when alternate agents are available. Parenteral fosfomycin is not available in the US, but for areas of the world where this agent is available, it is a reasonable option for invasive CRE infections. In addition, there are a number of potential CRE-active agents in advanced phases of drug development.

In conclusion, effectively treating CRE infections remains a daunting challenge. Judicious use of antibiotics and proper infection control practices are the cornerstones to decreasing their emergence and transmission.

Written by: Brian Chow, MD

Effectiveness of the influenza vaccine is a perennial question and is monitored and estimated yearly in multiple networks worldwide, including through the CDC sponsored Influenza Vaccine Effectiveness (Flu VE) Network in the U.S. VE is affected by a number of factors, chiefly the antigenic similarity between the strains contained in the annual vaccine (A/H3N2, A/H1N1, and B) and the circulating strain or strains. Patient-centered factors, however, also affect vaccine performance, including age (young and old), health status, and type of vaccine received.

Interim analyses from the Flu VE Network show that for 2015-16, VE is nearly 60% (http://www.cdc.gov/media/releases/2016/flu-vaccine-60-percent.html), an improvement over last year’s vaccine, which had a VE of 23%. The dominant circulating strain this year is the A/H1N1pdm09 virus, which has remained antigenically stable since the 2009 pandemic, whereas the dominant circulating strain last season was A/H3N2 which was a strain antigenically different from the vaccine strain. The theme of lower VE against A/H3N2 compared to A/H1N1pdm09 recurs in multiple studies.

A recently accepted meta-analysis of VE assessed in studies utilizing the test-negative design showed notable differences between A/H3N2 and A/H1N1pdm09 strains(1). The test-negative design is a validated form of a case-control design that evaluates patients presenting with illness, assesses vaccination status, and obtains laboratory confirmation of disease. Odds of influenza positive tests are then compared in vaccinated and unvaccinated groups to estimate VE. The meta-analysis of VE by Belongia and colleagues shows lower VE against A/H3N2 compared with A/H1N1pdm09 in all age groups, including children, over multiple seasons.

One year ago in the February 2015 meeting, the ACIP removed the preferential recommendation for live attenuated influenza vaccine (LAIV) for children age 2 to 8 years. This recommendation was initially put into place based on data from randomized clinical trials showing superior immunogenicity of the LAIV products compared to standard inactivated influenza vaccine (IIV)(2). Comparative studies of VE of LAIV and IIV published recently in Pediatrics and Vaccine, however, have cast doubt on the superiority of LAIV. Using data from four seasons, two years with predominantly A/H1N1pdm09 strains, and two predominantly A/H3N2 strains, Chung and colleagues report in Pediatrics that VE of LAIV against pandemic A/H1N1pdm09 was inferior to IIV, but similar between the two types of vaccines for A/H3N2 and type B (3). These finding were confirmed in Caspard and colleague’s study in Vaccine (4). The findings may be explained by reduced thermal stability of the viral construct for the A/H1N1pdm09 vaccine strain in the LAIV vaccine, leading it to be more susceptible to degradation with deviations from appropriate cold chain handling.

Issues of priming and repeat vaccination and influenza VE continue to be investigated. In the March issue of PIDJ, Thompson and colleagues investigate the effects of prior season vaccination and priming in children (5). Priming is defined as 2 doses of vaccine in a single prior season, with alternative definitions of priming also examined. VE was consistently higher when children had received 2 doses of an influenza vaccine in a prior season. Authors also report some carry over protection in the range of 36-40% vaccine effectiveness against A/H3N2 for children vaccinated in the previous season. A carry over effect from prior seasons was also seen in Ohmit’s study in JID of influenza household contacts (6).

Two recent studies in older adults raise concern that statin medications could impair influenza vaccine response and effectiveness. A post hoc analysis of a clinical trial data by Black and colleagues investigating response to an adjuvanted influenza vaccine (7) found lower post-vaccination geometric mean titers in statin users compared to non-users. The second study by Omer and colleagues conducted in a large HMO showed reduced influenza VE against medically attended acute respiratory illnesses among statin users compared to nonusers (8). Laboratory confirmation of influenza illness was not used in this study. These hypothesis-generating studies may not have direct impact on the majority of our pediatric patients, but could potentially affect their caregivers and household contacts.

As influenza vaccine effectiveness studies refine our understanding of who is at risk for reduced vaccine effectiveness, the data remain consistent on one aspect—annual influenza vaccination is still the most effective way to protect against illness. Parents should be counseled that we cannot predict which strain will dominant in a given season, so vaccination with the current strain is warranted. The vaccine may also give protection should type B co-circulate. Additionally, even with some residual protection from the prior year’s vaccine, an annual vaccine is necessary to assure the best protection against influenza.

1. Belongia EA, Simpson MD, King JP, Sundaram ME, Kelley NS, Osterholm MT, et al. Variable influenza vaccine effectiveness by subtype: a systematic review and meta-analysis of test-negative design studies. The Lancet Infectious Diseases. 2016;In press.
2. Ashkenazi S, Vertruyen A, Aristegui J, Esposito S, McKeith DD, Klemola T, et al. Superior relative efficacy of live attenuated influenza vaccine compared with inactivated influenza vaccine in young children with recurrent respiratory tract infections. Pediatr Infect Dis J. 2006 Oct;25(10):870-9.
3. Chung JR, Flannery B, Thompson MG, Gaglani M, Jackson ML, Monto AS, et al. Seasonal Effectiveness of Live Attenuated and Inactivated Influenza Vaccine. Pediatrics. 2016 Feb;137(2):1-10.
4. Caspard H, Gaglani M, Clipper L, Belongia EA, McLean HQ, Griffin MR, et al. Effectiveness of live attenuated influenza vaccine and inactivated influenza vaccine in children 2-17 years of age in 2013-2014 in the United States. Vaccine. 2016 Jan 2;34(1):77-82.
5. Thompson MG, Clippard J, Petrie JG, Jackson ML, McLean HQ, Gaglani M, et al. Influenza Vaccine Effectiveness for Fully and Partially Vaccinated Children 6 Months to 8 Years Old During 2011-2012 and 2012-2013: The Importance of Two Priming Doses. Pediatr Infect Dis J. 2016 Mar;35(3):299-308.
6. Ohmit SE, Petrie JG, Malosh RE, Johnson E, Truscon R, Aaron B, et al. Substantial Influenza Vaccine Effectiveness in Households With Children During the 2013-2014 Influenza Season, When 2009 Pandemic Influenza A(H1N1) Virus Predominated. J Infect Dis. 2016 Apr 15;213(8):1229-36.
7. Black S, Nicolay U, Del Giudice G, Rappuoli R. Influence of Statins on Influenza Vaccine Response in Elderly Individuals. J Infect Dis. 2015 Oct 28.
8. Omer SB, Phadke VK, Bednarczyk RA, Chamberlain AT, Brosseau JL, Orenstein WA. Impact of Statins on Influenza Vaccine Effectiveness Against Medically Attended Acute Respiratory Illness. J Infect Dis. 2015 Oct 28.

Written by: Ann-Christine Nyquist, MD, MSPH

It is election season in the United States and as Super Tuesday is upon us there may be some who are thinking of a moving to Canada if they are unhappy with the ultimate voting results or if they want to get away from campaign ads and robo calls. Not only does Canada entice as a political sanctuary but after you read the latest edition of The Journal of Pediatric Infectious Disease Society you might adopt some of the medical practice guidelines of the Canadians based on an interesting report from Brazil.

de Almeida Torres et al report an epidemiologic investigation and the management of contacts of a 7-year-old patient in Brazil who died with group A streptococcal (GAS) necrotizing fasciitis associated with toxic shock syndrome (1). 105 contacts had throat swabs cultured for GAS strains followed by emm typing and antimicrobial susceptibility testing. Virulence determinants were determined with PCR and sequencing. The authors report isolating from the patient’s wound culture a M1T1 GAS clone susceptible to all antibiotics tested. This same isolate was found in the throat of 36% of close contacts who had greater than 24 hours’ exposure to the index patient in the week prior to illness. The mother and two brothers were symptomatic with pharyngitis. The 29-year-old mother and 6-year-old brother were culture positive for the same GAS clone as the index patient but the 5-year-old brother who was also symptomatic with pharyngitis had a throat culture after the initiation of antibiotics. The father was without symptoms and his throat culture was negative. Expansion of the contact investigation identified 8 of 38 school and classroom contacts who had the same GAS emm type 1 clone on their throat cultures. None of the healthcare workers who cared for the patient had positive GAS throat cultures. Contacts who had GAS positive throat cultures were treated with oral amoxicillin. In addition to throat culture evaluation of contacts, an information campaign to educate about early signs and symptoms of GAS disease was initiated within 24 hours of the death of the index patient. After two months of follow-up there were no additional cases of invasive GAS detected.

Invasive GAS disease has been more frequently reported since the 1980s with seasonal peaks noted from December through March. Clinical manifestations include necrotizing fasciitis, bacteremia, meningitis, septic arthritis, pneumonia with or without empyema, and strep toxic shock syndrome. Risk factors in children include varicella and other skin lesions, influenza, crowding, lower parental income and education. For adults their primary risk factor is exposure to children. The incidence of invasive GAS in children ranges from 0.5 to 5.0 per 100,000 population depending upon age and country. Aboriginal populations have had the highest incidence up to 75 per 100,000 population. According to the 2014 provisional report of the Active Bacterial Core Surveillance (ABCs) Emerging Infections Program the national estimates of invasive GAS cases in all age groups are 4.4/100,000 population averaging 3.96/100,000 population over the last five years (2).

Antimicrobial chemoprophylaxis is routinely recommended for close contacts of cases with N. meningiditis and for H. influenzae type b household contacts if the household has a child less than 4 years of age who is not fully vaccinated. The estimates of number needed to treat (NNT) or provide prophylaxis to prevent one meningococcus case is 200 contacts and for H. influenzae type b cases ranges from 50 to 200 contacts. Risk of GAS infection of close contacts of index patients with invasive GAS infection and the potential value of antibiotic prophylaxis to prevent these infections is unclear and recommendations from different countries are divergent. Based on a US study in the late 1990’s, providing antimicrobial prophylaxis to 750 household contacts would prevent one secondary case of invasive GAS (3).

In 2002, a CDC expert panel did not recommend routine screening for or chemoprophylaxis against GAS for household contacts of index patients with invasive group A streptococcal disease, but they stated that “providers may choose to offer prophylaxis to household contacts who are at increased risk of disease or mortality” (4). This panel did recommend enhanced surveillance and isolate storage with epidemiological investigation initiated in the event of two or more cases of nosocomial postpartum or postsurgical invasive GAS infections caused by the same strain.

This study from Brazil doesn’t conclude whether antibiotic prophylaxis is effective but provides additional recommendations and supportive data regarding invasive GAS epidemiology. The authors recommend antibiotic treatment to close contacts who have been exposed to an index patient for greater than 24 hours per week before the initial disease onset, inclusive of household contacts and school contacts.

So what is a US voter in a quandary to do ... I say vote for the Canadians ... or maybe the Australians.

Since 2006, the Ontario Group A Streptococcal Study Group has recommended that antibiotic prophylaxis with an oral cephalosporin be offered to all household contacts who were in close contact with the index patient with severe invasive GAS infection within the week before the onset of illness (5). A recently published prospective observational study from Australia made the more robust case for routine antibiotic prophylaxis for household contacts of cases regardless of severity of illness (6).

Let’s vote for a new path and align with our Canadian, Australian, and Brazilian colleagues.

We should carefully discuss management options and risks and invasive GAS surveillance with the family, including the possible option of antibiotic prophylaxis for all household contacts of any patient with invasive GAS disease.

I am Chris Nyquist and I approve of this message.


  1. de Almeida Torres RSL, dos Santos TZ, de Almeida Torres RA, et al. Management of Contacts of Patients With Severe Invasive Group A Streptococcal Infection. J Pediatr Infect Dis Soc 2016; 5: 47-52. DOI:10.1093/jpids/piu107.
  2. Centers for Disease Control and Prevention. 2014. Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Group A Streptococcus, provisional report—2014. Available via the internet: http://www.cdc.gov/abcs/reports-findings/survreports/gas14.pdf. Accessed February 26, 2016.
  3. Robinson KA, Rothrock G, Phan Q, et al. Risk for severe group A streptococcal disease among patients’ household contacts. Emerg Infect Dis 2003;9:443-7.
  4. Prevention of invasive group A streptococcal disease among household contacts of case patients and among postpartum and postsurgical patients: recommendations from the Centers for Disease Control and Prevention. Clin Infect Dis 2002;35:950-9.
  5. Public Health Agency of Canada. Guidelines for the prevention and control of invasive group A streptococcal disease. Can Commun Dis Rep Wkly 2006;1-32.
  6. Carapetis JR, Jacoby P, Carville K, et al. Effectiveness of clindamycin and intravenous immunoglobulin, and risk of disease in contacts, in invasive group A streptococcal infections. Clin Infect Dis 2014;59:358-65.

CDC has issued “Interim Guidelines for Preventing Sexual Transmission of Zika Virus” and “Updated Interim Guidelines for Health Care Providers Caring for Pregnant Women and Women of Reproductive Age with Possible Zika Virus Exposure.”

Written by: Pui-Ying Iroh Tam, MD

When is the testing that we do too much? This is not at all a novel issue, but a dilemma that physicians have long voiced. In fact, in 2012, 42% of US primary care physicians believed that patients in their own practices were receiving too much care, which occurred most commonly as a result of malpractice concerns (76%), clinical performance measures (52%), and inadequate time to spend with patients (40%) [1].

Recently, I consulted on an 11 month-old male who had been transferred from a rural hospital with several days of fever and an expanding rash that began on his buttocks. On exam he was noted to have red, cracked lips, but there was no bulbar conjunctival injection, nor any of the other features of Kawasaki disease. Most notable were the targetoid lesions on his face, chest and trunk, which were clearly evident at the time of our involvement in his care.

Given the history of sick contacts in the household, and mindful also of the rare but fatal adverse effects of intravenous immunoglobulin therapy that I had personally witnessed, I elected further testing to investigate for infectious causes such as mycoplasma and herpes simplex virus, among others. I had thought that my workup would help rule out other potential etiologies and would bring clarity to the management of an infant with possible atypical Kawasaki. However, when the next attending came on-service a few days later, all the pending tests proved to be more of an encumbrance than an assistance, since the consult team now felt bound to follow up on the results – though my more experienced colleague felt quite certain that the patient had Kawasaki.

The healthcare costs that have been generated as a result of overtesting are increasing and unsustainable: in 1980, costs were $253 billion, in 1990 it was $714 billion, and in 2008 it was $2.2 trillion [2]. Out of this, excessive testing is believed to cost $200-250 billion per year [3]. One paper examining high-value cost-conscious care provided a list of 37 clinical situations in which a test did not reflect high-value care. The six relevant infectious disease scenarios included [2]:

  1. Serologic testing for suspected early Lyme disease;
  2. Serologic testing for patients with chronic nonspecific symptoms and no clinical evidence of disseminated Lyme disease;
  3. Performing sinus imaging studies for patients with acute rhinosinusitis in the absence of predisposing factors for atypical microbial causes;
  4. Performing pre-discharge CXR for hospitalized patients with community-acquired pneumonia who are making a satisfactory clinical recovery;
  5. Obtaining CT scans in patients with pneumonia that is confirmed by CXR in the absence of complicating clinical or radiographic features; and
  6. Performing follow-up imaging studies of incidentally discovered pulmonary nodules ≤4 mm in low-risk individuals.

However, if we expanded this to other aspects of pediatric infectious diseases practice, should we not also include in the list of unnecessary overtesting: daily complete blood count with differentials and inflammatory markers in patients who are making a satisfactory clinical recovery; the ordering of both C-reactive protein and erythrocyte sedimentation rate tests in patients with suspected illness, infection or inflammation; or even the repetitive ordering of blood cultures for febrile patients after the first several sets are negative? If one accounts not only for excessive testing but also follow up testing for unnecessary diagnostic tests and procedures, as well as extra days in the hospital, nearly one-third of all healthcare spending – or $800 billion – is wasted [3], without arguably an improvement in clinical outcomes.

With this patient one could fault the numerous studies I requested, which all ended up being negative, as prevarication. Eventually, intravenous immunoglobulin therapy was administered to the patient, who rapidly defervesced, clinically improved and was discharged soon after. In retrospect, the reasoning behind the workup could be attributed to all the survey responses listed above, as well as by my limited experience [4], particularly compared to that of my older colleague. As a specialty that relies heavily on diagnostic testing to manage and follow our patients, we are as much bound by the need to consider high-value, cost-conscious care as other physicians. In the primary care survey, 76% of respondents stated that they were interested in learning how aggressive or conservative their own practice style was compared with that of other physicians in their community [1]. This openness and receptivity is something that we as a specialty should also be cognizant of, and the findings of which we should strive to address, for the sake of our patients.


  1. Sirovich BE, Wooshin S, Schwartz LM. Too Little? Too Little? Too Much? Primary care physicians' views on US health care: a brief report. Arch Intern Med. 2011 Sep 26;171(17):1582-5. doi: 10.1001/archinternmed.2011.437.
  2. Qaseem A, Alguire P, Dallas P, Feinberg LE, Fitzgerald FT, Horwitch C, Humphrey L, LeBlond R, Moyer D, Wiese JG, Weinberger S. Appropriate use of screening and diagnostic tests to foster high-value, cost-conscious care. Ann Intern Med. 2012 Jan 17;156(2):147-9. doi: 10.7326/0003-4819-156-2-201201170-00011.
  3. Reuters. American College Of Physicians Tackles Issue Of Excessive Medical Testing. 7 December 2015. http://www.huffingtonpost.com/2012/02/16/american-college-of-physicians-medical-testing_n_1281277.html. Accessed 7 Dec 2015.
  4. Grady D. Reasons for overtreatment: comment on "Too little? Too much? Primary care physicians' views on US health care". Arch Intern Med. 2011 Sep 26;171(17):1586. doi: 10.1001/archinternmed.2011.461.

Written by: Galit Holzmann-Pazgal, MD

Zika virus is a previously relatively unknown flavivirus. Originally discovered in 1947 in the Zika forest of Uganda when a rhesus monkey developed infection, it was subsequently reported only sporadically in humans from 1951-1981 via serologic evidence in people from multiple African countries and parts of Asia.

The first large outbreak outside of Africa and Asia was reported in 2007 in the Federated States of Micronesia. Illness was relatively mild consisting of rash, arthralgia and conjunctivitis. Subsequently, the virus spread further, and an outbreak was reported in French Polynesia in 2013. This outbreak was characterized by more severe illness including neurologic and autoimmune complications such as Guillain Barré syndrome.

In 2014, localized (autochthonous) transmission was first reported in Chile (Easter Island). In 2015, Brazil confirmed autochthonous transmission with subsequent spread within the country and in late 2015, reported a 20 fold annual increase in cases of newborns born with microcephaly linked to maternal infection with Zika virus during pregnancy. The virus was also determined to be spreading throughout Central and South America. In December of 2015, the first confirmed case of Zika virus locally transmitted in Puerto Rico was confirmed, and in January of 2016 the first U.S. case of a newborn born with microcephaly due to Zika virus infection was reported in Hawaii. That infant’s mother likely became infected in Brazil. No autochthonous transmission in the United States has been reported to date.

Zika virus is spread via the bite of the Aedes species of mosquitos, particularly Aedes aegypti, the same mosquito responsible for the spread of Dengue and Chikungunya in the Americas. It is a single stranded RNA flavivirus related to Dengue, Yellow Fever and West Nile Virus. Additional routes of transmission include perinatal and in utero. There are also reports of Zika virus RNA in blood and semen with solitary reports of possible sexual and transfusion related transmission.

The symptoms of Zika virus infection include fever, headache, malaise, arthralgia/myalgia, maculopapular pruritic rash and conjunctivitis. Many of these symptoms are similar to Dengue and Chikungunya but are typically milder. Severe disease is rare. It is estimated that 1/5 infected people will develop symptoms. The incubation period ranges from a 2-7 days and duration of illness is usually just a few days but can last up to a week.

Diagnosis can be made via RT-PCR on acute phase samples (within a week of symptom onset). In addition, serology can be performed. IgM testing should be done > 4 days after symptom onset. As Zika virus typically occurs in areas with other mosquito borne illnesses such as Dengue and Chikungunya, these infections must also be considered in the differential of symptomatic patients and returning travelers. Diagnosis can be complicated by cross reactivity of Zika virus antibodies with other flaviviruses.

Testing is available via the CDC or some state health departments. Information can be found at http://www.cdc.gov/zika/hc-providers/diagnostic.html. An algorithm specifically for testing of pregnant women with potential exposure to Zika virus has recently also been released by the CDC. http://www.cdc.gov/mmwr/volumes/65/wr/mm6502e1er.htm 

Care of infected individuals is supportive. There are no currently available antivirals or vaccine available for Zika virus.

At this time, there are CDC travel alerts (level 2) to areas of the world with ongoing local transmission of Zika virus. Travel to these areas is discouraged for pregnant women and steps to avoid mosquito bites should be taken in affected geographic locations. http://wwwnc.cdc.gov/travel/notices

In conclusion, Zika virus is an emerging pathogen with rapidly spreading global significance. Since the vector of spread, the Aedes mosquito, is found throughout the world and is common in urban areas with dense populations, the virus is likely to continue spreading through both South/Central America and possibly the Southern United States.


  1. Hayes EB, Zika virus outside of Africa. Emerging Infectious Diseases 2009 Sep; 15(9):1347-50.
  2. Zika virus outbreaks in the Americas. Wkly Epidemiol Rec. 2015 Nov 6; 90(45): 609-10.
  3. www.cdc.gov/Zika

The CDC, in consultation with the American Academy of Pediatrics, has developed interim guidelines for the evaluation, testing, and management of infants born to mothers who traveled to or resided in an area with Zika virus transmission during pregnancy. The document provides guidance to healthcare providers caring for 1) infants with microcephaly or intracranial calcifications detected prenatally or at birth or 2) infants without these findings whose risk is based on maternal exposure and testing for Zika virus infection.

Pediatric healthcare providers should ask mothers of newborns with microcephaly or intracranial calcifications about their residence and travel while pregnant and about any symptoms of illness compatible with Zika virus disease (acute onset of fever, rash, joint pain, and red eyes). Healthcare professionals should also obtain the results of any Zika virus testing performed before the mother gave birth.

The Interim guidelines recommend that doctors and their teams consider possible clinical issues when caring for infants who might have been infected with Zika virus infection. For example, cranial ultrasound is recommended for all infants with possible Zika virus infection unless prenatal ultrasound results in the third trimester demonstrated no brain abnormalities. Also recommended for all infants with possible Zika virus infection, regardless of symptoms, are repeat hearing screening and developmental monitoring.

Treatment of Zika virus infection in babies is supportive and should address the infant’s specific needs. Investigations are ongoing to better understand what services will be most appropriate for affected children as they grow.

These interim guidelines will be updated as more information becomes available.

The guidelines can be found here: http://dx.doi.org/10.15585/mmwr.mm6503e3er 

Please forward to other colleagues as appropriate. If you have additional questions related to Zika virus, please contact CDC-Info at 1-800-CDC-Info or http://www.cdc.gov/cdc-info/.

Written by: Janet Gilsdorf, MD, FPIDS

As 2015 slips behind us, it’s a good time to reflect on the many successes of the Pediatric Infectious Diseases Society over the past year. Our journal, JPIDS, was accepted for MEDLINE indexing, meaning ...

Written by: Gregory P. DeMuri, MD

Article Summary

In the December issue of the Journal of the Pediatric Infectious Diseases Society Koningstein and colleagues report the results of an epidemiological study of extended-spectrum-cephalosporin-resistant (ESC-R) Escherichia coli in day-care centers in the Netherlands.1 This study was performed over a 22 month period from 2010-2012 in 44 different day care centers throughout the country. It was conducted as a part of a national prospective cohort study of infectious diseases in day care centers. Stool samples were taken from randomly assigned attendees monthly and cultured for E. coli. Isolates were screened for ESC-R using disk diffusion testing and confirmed by PCR. In addition, demographic and environmental risk factors were studied.

Overall, 852 stool samples were analyzed from the study population. The mean age of sampled children was 20 months. The authors found that 38 of 852 (4.5%) of children were colonized with ESC-R E.coli. There was a trend for an increase in the prevalence during the first part of the study compared to the second: 3.2% in 2010-2011 and 5.8 % in 2012 though the results did not achieve statistical significance. The majority of ESC-R E. coli strains detected contained blaCMY-2, blaCTX-M-1, or cAmpC mutations. Significant risk factors for ESC-R colonization in day care center attendees were: age < 1 year old, attending centers where paper towels were available, restricting ill children from attending day care, performing extra checks on handwashing of ill children, and always reporting notifiable diseases to local health authorities. The authors conclude that day care attendance leads to exposure to both colonizing agents such as ESC-R E. coli and community –associated pathogens such as respiratory viruses, resulting in the higher chances of receiving antibiotic treatment, which may impact on ESC-R carriage, especially in infants. They call for further study of day care practices to prevent colonization and infection with these organisms.


This study caught my attention after I consulted on a 6 month old infant who had been admitted to the hospital for a febrile UTI secondary to E. coli. The infant had been treated with an oral cephalosporin and then admitted when susceptibility testing showed resistance to all cephalosporins, and all oral agents. She was treated with a course of meropenem and discharged. What is a bit disturbing is that she had no traditional risk factors for a multi-drug resistant organism; no prior illnesses and no prior antimicrobial exposure. She did, however, attend day care. What should have been treatable with an oral antimicrobial required several days of inpatient IV therapy.

In this investigation about 5% of children attending day care harbored ESC-R E. coli in the stool and a trend in increased detection was observed over the 22 month study period. This study has several limits in interpretation. First, it was done in the Netherlands and the results may not apply to other populations of children. Secondly, this was a study of colonization as all study subjects were asymptomatic. The rate of drug resistance in invasive strains might be different. In addition, children not attending day care were not included as controls. Nonetheless the results are concerning. In this same issue of JPIDS Stillwell et al describe an outbreak of KPC-3 carbapenem resistant Klebsiella pneumoniae in a US pediatric hospital.2 Also in this issue Drew et al studied 551 isolates of ESBL for the UK producing Enterobacteriaceae and found extensive associated antimicrobial resistance in these isolates and the only consistent antibiotic class to which the isolates remained susceptible were the carbapenems.3

Children in day care settings tend to be the canaries in the coal mine for pediatric infectious diseases. The detection of antibiotic resistant, gram-negative organisms in presumably healthy children is disturbing. Further epidemiologic studies are needed to track these organisms and to determine effective means of controlling spread in the population. Meanwhile the results of this study may suggest that in the near future we will treat more and more “community acquired” multidrug-resistant, gram-negative infections in children.


  1. Koningstein M, Leenen MA, Mughini-Gras L, et al. Prevalence and Risk Factors for Colonization With Extended-Spectrum Cephalosporin-Resistant Escherichia coli in Children Attending Daycare Centers: A Cohort Study in the Netherlands. J Pediatric Infect Dis Soc 2015;4:e93-9.
  2. Stillwell T, Green M, Barbadora K, et al. Outbreak of KPC-3 Producing Carbapenem-Resistant Klebsiella pneumoniae in a US Pediatric Hospital. J Pediatric Infect Dis Soc 2015;4:330-8.
  3. Drew RJ, Ormandy EE, Ball K, et al. Antimicrobial Susceptibility Patterns Among Extended-Spectrum beta-Lactamase-Producing Enterobacteriaceae in a Large Pediatric Hospital in the United Kingdom. J Pediatric Infect Dis Soc 2015;4:e147-50.

Written by: Saul R. Hymes, MD

It’s becoming a late November tradition: rake the last of the leaves before winter; reserve the Turkey at the butcher; engage in one of the largest worldwide media, social media, education and advocacy events around antibiotic resistance and judicious antibiotic use...wait, what?

Since 2008, the Centers for Disease Control and Prevention (CDC) has organized an annual week-long set of activities aimed at increasing awareness about antibiotic resistance (which, if you don’t know by now, is a huge problem) and antimicrobial stewardship under the auspices of their existing year-round Get Smart program, led by Lori Hicks, DO. The observance of this so-named Get Smart Week (this year from November 16-22), in the CDC’s own words,

...is a key component of CDC’s efforts to improve antibiotic stewardship in communities, in healthcare facilities, and on the farm in collaboration with state-based programs, nonprofit partners, and for-profit partners. The one-week observance raises awareness of the threat of antibiotic resistance and the importance of appropriate antibiotic prescribing and use.

Every year the program attracts more partners and more followers and this year seemed to cross a threshold in two important ways. While Get Smart Week has often coincided with similar day-long or week-long events in other countries (European Antibiotic Awareness Day, Australia's Antibiotic Awareness Week), this year was the first year that it coincided with a new World Antibiotic Awareness Week sponsored by the World Health Organization (WHO). Additionally, for the first time ever, the week was made official by the White House, with President Obama proclaiming November 16-22, 2015 as Get Smart About Antibiotics Week.

It’s only fitting that this year’s week should be even bigger and more official than previous years—it’s been a banner year for antibiotic stewardship in general, with the initiation of the Combatting Antibiotic Resistant Bacteria (CARB) Action Plan and Advisory Council, The White House Forum on Antibiotic Stewardship, and impending rules by CMS and JCAHO requiring antimicrobial stewardship programs of various types of hospital facilities. But the best part about Get Smart Week, and the thing that really makes it run, is the activities—by all of its official partners and also by all of us. So how can we all Get Smart ourselves and help others do the same?

If your hospital is a member of the SHARPS group, it may be involved in activities for Get Smart Week. SHARPS is a multi-center data-sharing and QI collaborative formed to improve antimicrobial prescribing and stewardship and co-led by Jason Newland, MD, MEd; Adam Hersh, MD, PhD; and Jeff Gerber, MD, PhD, MSCE. Many of the SHARPS institutions put up posters, organize educational sessions, make t-shirts and pins, and in other ways raise the awareness of antimicrobial stewardship at their hospitals. Even if your hospital isn’t a SHARPS institution, or if you aren’t based at a single hospital, you can very easily use the pre-made flyers, posters, and other materials the CDC makes available on their Get Smart website to put together a local awareness and education campaign. And who among us doesn’t have some slides about antibiotics or antibiotic resistance? Choose Get Smart Week to give that lecture to your medical students or residents.

But if you’re a PIDS member (and chances are good that if you’re reading this, you are), you’re already a contributor, at least a little, as PIDS was an official partner in Get Smart Week this year. PIDS participated in a global twitter chat on Wednesday, November 18, and was in the top ten for most tweets during both the 2-hour chat period as well as the for the entire day. PIDS also co-led a twitter chat on Friday, November 20th, focusing on antibiotic use in animal agriculture. This topic received further emphasis this year, with all of Friday devoted to activities designed to educate on the issue, and the early release during the week of a report by the AAP on the pediatric impact of antibiotics used in animal agriculture.

The Twitter chats deserve further special mention, as this is an opportunity for all to get involved in Get smart Week in a very easy and high impact way. We have already seen the potential role for social media in medicine discussed here in PIDSNews; but more than a research tool, social media can be a powerful avenue for advocacy, education, and outreach. The CDC itself provides a social media toolkit to partners and encourages participation via Facebook posts or Twitter activity; and they measure the impact this activity has. Last year Get Smart Week generated over 60 million individual impressions—the number of times someone viewed a Get Smart Week-related social media message. This year the Twitter activity alone on one single global twitter chat day (November 18th) led to over 163 million impressions. At 27,000 impressions averaged among each of the 6,000 participants, that’s far more people than any of us could hope to reach in a lifetime of practice or local stewardship efforts.

This year’s Get Smart Week has drawn to a close but hopefully, for next year, some of you reading this will be inspired: to organize activities at your institutions, to join Twitter and join the social media conversation, and in general to advocate as broadly as possible to our fellow physicians, governments, and the public to Get Smart about antibiotics.

Dear PIDS members:

The information recently forwarded by IDSA and HIVMA regarding alternative sources of pyrimethamine for treatment of toxoplasmosis contains a link to order pyrimethamine + leucovorin from Imprimis, a compounding pharmacy. Please note IDSA, HIVMA and PIDS are not endorsing any particular medication or pharmacy for alternative treatments for toxoplasmosis.

The order form from Imprimis lists six fixed combination ingredient formulations, all pills, containing pyrimethamine + leucovorin.

The recommended* treatment for congenital toxoplasmosis is:

  • Pyrimethamine: 1 mg/kg every 12 hours orally for 2 days; followed by 1 mg/kg once per day orally for 2 or 6 months; followed by 1 mg/kg once per day every Monday, Wednesday, Friday
  • Sulfadiazine: 50 mg/kg every 12 hours orally
  • Folinic acid (leucovorin): 10 mg three times weekly orally

The total duration of treatment usually is one year.
*Long/Pickering/Prober, Principles and Practice of Pediatric Infectious Diseases, 4th edition, Table 273-1.

While the fixed combinations of pyrimethamine and leucovorin contained in the Imprimis pills will not provide the correct doses of both drugs for young children, Imprimis is able to compound liquid formulations with specified amounts of pyrimethamine and leucovorin to meet the required doses for an individual baby.

Compounded products are not subject to approval by the U.S. Food and Drug Administration, but may be appropriate for individual patient use. As with treating any condition, providers will need to evaluate the most appropriate treatment option on a case-by-case basis in consultation with their patients. More information on pharmaceutical compounding is available from the American Pharmaceutical Association.

If you have difficulty obtaining the drug for your young patients, we suggest you call Imprimis 866-551-7195 (toll-free) or work with the pharmacists at your institution to understand the best options for obtaining appropriate liquid formulations.

How do we overcome the mindset of anti-vaccinators, a.k.a. anti-vaxers? I sat down with Adam Strasberg1, a political strategist and ad creator, to discuss how to improve the medical community’s approach to vaccine advocacy. He gave me new perspectives on the issue with insights on behavioral economics, ethnography, and the mindset of the lay person.

  1. Brute force does not work. Drilling more science into the minds of college-educated anti-vaxers does not work and may actually produce contradictory results. Nyhan et al. recently published two articles showing current scientific-based public health communications may actually increase misperceptions or reduce vaccination intention with MMR and influenza vaccine.
  2. Emotions matter. Communication is more than just about being on message. Personal stories influence more than the scientific data. Emotions move more than facts. The rise of social networks, blogging and instant internet access on handheld devices has empowered all-comers to tell their stories. Professional degrees are not needed, and are often a hindrance to telling good stories. We, as doctors, need to improve our story-telling techniques. To support the science, we also need to talk about the college freshman we cared for who was left without legs from meningococcal infection or the 6 year old boy who died from the “strangling angel” diphtheria this year in Spain. Stories are emotion delivery vehicles.
  3. Young pediatricians need more experience. Because our vaccines have been so successful, graduating pediatricians today have never seen chicken pox let alone polio or measles. How can they powerfully tell stories about patients they have never cared for? Some effective ways to stir emotion in our trainees beyond lecturing and showing pictures are: 1) Send them abroad. One case of neonatal tetanus or watching a child die from Hib meningitis knowing that the illness was preventable by vaccination will remain etched in their memories for a lifetime. 2) Bring all of your trainees to see the child with exposed muscle following surgery for group A strep necrotizing fasciitis. Remind them that these patients were common before the varicella vaccine. Take them to the pertussis baby on ECMO in the PICU. All trainees should at least see the pertussis cough video. 3) Bring in patients who have recovered from meningococcemia or dealt with HPV and cervical cancer to talk about their experiences. Our trainees understand the science but they will be better vaccine promoters if they also understand the emotions.
  4. Community immunity. Belonging to a community can be a powerful motivator. Everyone wants to be a part of a community. Members of a community feel responsible to help and contribute to their community. Using the phrase “herd immunity” creates the wrong frame for anti-vaxers. A herd follows unthinkingly; most anti-vaxers do not want to be part of a herd. The terminology should be changed to “Community Immunity,” to incite a sense of belonging and purpose.
  5. Mother vaccine spokesperson wanted. We need to reconsider how the medical profession is delivering the message on vaccines. Currently, pro-vaccine spokespersons are experienced male doctors who are revered in the scientific world for their enormous contributions to vaccine science. However, anti-vaxers frequently view them as patriarchs in a social system in which males hold primary power. Anti-vaxers are often young, educated new mothers who want no part of this historically patriarchal society. While there is value in male physicians providing vaccine guidance, the pro-vaccine messages additionally should be articulated in our media sources by women who are mothers as well as doctors. They can more effectively start the discussion with, “I know that you want to do what is best for your children...”
  6. Understand what drives Anti-Vaxers. We continue to speak of vaccination as a public health and science issue, despite the inability of those constructs to influence anti-vaxers. Instead of speaking to parental rights, perhaps we should focus more on protecting innocent children. Instead of promoting science, we should emphasize the naturalness of the vaccination process – it is not a scientific or artificial occurrence, but a natural one, akin to lifting weights to get stronger. We need more research to understand the levers that move anti-vaxers so we can learn to speak with metaphors and constructs that influence them to reconsider their objections. Our children deserve it!

Written by: Pia S. Pannaraj, MD, MPH
Children's Hospital Los Angeles

1 Adam Strasberg is the son of acting teachers. He was raised in the world of actors, theatre and books. With an MFA from NYU Graduate Film School, Adam eschewed the bright lights of Hollywood, instead finding his element fusing his creative talent with his desire for social change inside the world of politics. He is a partner at a marketing consulting firm in Washington, DC. He can be reached at This email address is being protected from spambots. You need JavaScript enabled to view it.

Article summary
In the June issue of the Journal of the Pediatric Infectious Diseases Society, Schwartz and colleagues describe their experience with invasive fusariosis, a relatively rare but often fatal infection. This is a retrospective review of all cases of culture-proven, invasive Fusarium in immunocompromised children at a large, tertiary care facility from 1996-2011. Of 13 children at the authors' institution with positive cultures for Fusarium species, 5 were immunocompromised hosts with invasive infection. Four of the 5 children described previously underwent hematopoietic stem cell transplant (HSCT) with subsequent prolonged neutropenia. All 5 cases had lung involvement, while 2 had skin findings, 2 had brain involvement, and 1 had a positive blood culture for Fusarium. All cases were treated with amphotericin B, while 3 also received voriconazole, and 1 child received granulocytes. Four of the cases were coinfected with bacteria, viruses, or other fungi. All 4 of the children who had undergone HSCT died, with Fusarium believed to be a contributing cause of death.

In addition to these 5 cases, the authors reviewed all reports of invasive Fusarium infections in children available in the literature, summarizing 33 published cases from 1973 to 2012. In this review, the skin (21 cases) was the most common site of infection, followed by blood (14) and lung (11), with brain (3) and sinuses (2) reported less frequently. Treatment was variable, though amphotericin was the most common antifungal used, reported in 25 cases.

Fusarium species are second only to Aspergillus spp. as the most frequent mold implicated in human infections, with invasive disease occurring almost exclusively in immunocompromised hosts. Given the high mortality rate, relative resistance to antifungals, and interspecies variability in susceptibility profiles, treatment of infections due to Fusarium spp. remains a challenge for both adult and pediatric infectious disease physicians. Furthermore, the paucity of available pediatric data introduces an added layer of difficulty in the management of these often complicated patients. In addition to nicely summarizing the available pediatric literature on invasive fusariosis, the article by Schwartz et al also reinforces some important features of Fusarium infections in children.

First, despite reports of the changing epidemiology of fungal infections in children and adults with cancer,1,2 invasive fusariosis remains an uncommon diagnosis. A previous retrospective study reported an overall incidence of ~6 cases per 1000 HSCT, higher in allogeneic compared to autologous transplants.3 While the present article does not report the local incidence, with only 5 cases in a 15 year period at a location with the highest number of new cancer diagnoses and HSCTs in Canada, it seems unlikely to be significantly higher than that previously reported. Second, the authors highlight the variability in treatment of these patients. Although the majority of children received amphotericin, there was inconsistency in the use of combination therapy and adjunctive therapies, such as granulocyte colony stimulating factor and granulocyte transfusion. Finally, it appears that although the prognosis remains poor we may be making progress. Mortality in this series remains high at 50%, but this is an improvement compared to 92% mortality rates reported less than 30 years ago.4 This is likely multifactorial, reflecting differences in the management of patients with malignancy, improvements in diagnostic techniques, changes in the use of antifungal agents, and overall advancements in medical care, among others.

Another noteworthy finding of this case series is the number of coinfections. In the 5 cases described by the authors, 4 had at least one other pathogen detected: 1 child had Staphylococcus aureus, 1 had Aspergillus fumigatus, 1 had both adenovirus and cytomegalovirus (CMV), and 1 had both CMV and Stenotrophomonas. Although a high rate of coinfection has been described in patients with invasive pulmonary aspergillosus5, this has not been widely studied in patients with fusariosis and may have potential implications for both the pursuit of additional diagnostic evaluation following detection of Fusarium spp. and empiric antimicrobial therapy.

Due to its infrequent occurrence and uncertain applicability of in vitro susceptibilities, the optimal management of patients with invasive fusariosis remains unclear. A number of questions have yet to answered, including the role of combination antifungals and adjunctive therapies, such as granulocyte transfusion. This article underscores the need for continued research into this often fatal disease in order to provide evidence-based recommendations for diagnosis and management. --Rebecca Wallihan, MD


  1. Ben-Ami R, Lewis RE, Raad, II, Kontoyiannis DP. Phaeohyphomycosis in a tertiary care cancer center. Clin Infect Dis. Apr 15 2009;48(8):1033-1041.
  2. Maron GM, Hayden RT, Rodriguez A, et al. Voriconazole prophylaxis in children with cancer: changing outcomes and epidemiology of fungal infections. Pediatr Infect Dis J. Dec 2013;32(12):e451-455.
  3. Nucci M, Marr KA, Queiroz-Telles F, et al. Fusarium infection in hematopoietic stem cell transplant recipients. Clin Infect Dis. May 1 2004;38(9):1237-1242.
  4. Richardson SE, Bannatyne RM, Summerbell RC, Milliken J, Gold R, Weitzman SS. Disseminated fusarial infection in the immunocompromised host. Reviews of infectious diseases. Nov-Dec 1988;10(6):1171-1181.
  5. Georgiadou SP, Kontoyiannis DP. Concurrent lung infections in patients with hematological malignancies and invasive pulmonary aspergillosis: how firm is the Aspergillus diagnosis? J Infect. Sep 2012;65(3):262-268.

It's been quite a year in vaccine news. The year has been full of triumphs and full of gloom – from the declaration of polio almost being eradicated in Africa1 to the return of vaccine-preventable diseases like measles in the United States2. We felt the palpable fear of acute flaccid paralysis due to enterovirus D683 to the media hysteria of Ebola. And we celebrated the achievements of vaccine immunologists with the successful trials of the Ebola vaccine4 while dealing with the mismatched prediction for last year's influenza season5. In many ways, the news has captured the entire cycle of public perception of emerging infectious diseases and vaccination – from fear to triumph to forgetfulness of the dangers of vaccine-preventable diseases to suspicion over the value of routine vaccination.

Although these cycles have always occurred throughout the history of modern vaccination, the events of the past 18 months have felt more jumbled as numerous emerging infectious diseases and vaccine-preventable diseases have dominated the public consciousness. And unfortunately, many children continue to suffer from vaccine-preventable diseases due to lack of access to vaccines or misguided parental mistrust6.

But maybe the tide of public opinion is shifting. In a recent survey from the Public Policy Institute of California, over 65% of California adults agreed that children should be vaccinated in order to attend public school7. This public sentiment, along with advocacy from California State Senator and Pediatrician Dr. Richard Pan, eventually culminated in the passage of SB277 in California eliminating public belief exemptions in children attending public school8. In doing so, they joined Mississippi and West Virginia as the only states that do not allow personal belief exemptions. As a California resident, I am amazed at this turn of events. It was only a few years ago, we were watching personal belief exemption rates rise, celebrity talking heads rallying against vaccination, vilification of the human papilloma virus vaccine, and erosion of confidence in the vaccine schedule. While there is still a vocal minority espousing many of these misguided sentiments, there appears to be a change in overall public opinion.

What caused this change? There's no doubt that the California measles outbreak was a major factor in raising awareness about vaccine-preventable diseases. In addition, the recent pertussis outbreaks in California reinforced the importance of vaccination and herd immunity. Finally, there was the general concern surrounding the West Africa Ebola outbreak, MERS-coronavirus, and Enterovirus-D68. Perhaps it was all of these fear-inducing events that led to change. There's no doubt that fear is a powerful motivator. Researchers recently demonstrated that the best strategy in changing people's minds about vaccination was to communicate the dangers of a child getting measles or mumps9. But fear to change minds can only accomplish so much for so long. The real challenge is to continue to affect change when people forget about the fear. This is why the efforts of advocates like Dr. Pan in passing SB277 are so important. This will lead to lasting public policy change to improve public health and to protect children from vaccine-preventable diseases. But the battle is not over. Anti-vaccine groups have already vowed to fight SB277 in the courts and at the ballot box. And they have already targeted individual lawmakers who supported the bill. Dr. Pan's efforts have been met with death threats and a petition to recall him.

In the end, our mission as PIDS members doesn't change: continue to advance the science of vaccines, continue to communicate the safety and efficacy of vaccines, and continue to advocate for common sense public policy to increase vaccination coverage. As we celebrate the 60th anniversary of the polio vaccine and the prospect of a polio-free world, let's press forward to achieving our goal of "Freedom from infections for all children". --David K. Hong, MD


  1. McNeil DGJ. A Milestone in Africa: No Polio Cases in a Year. The New York Times 2015 8/11/2015.
  2. Zipprich J, Winter K, Hacker J, et al. Measles outbreak--California, December 2014-February 2015. MMWR Morb Mortal Wkly Rep 2015;64:153-4.
  3. Greninger AL, Naccache SN, Messacar K, et al. A novel outbreak enterovirus D68 strain associated with acute flaccid myelitis cases in the USA (2012-14): a retrospective cohort study. Lancet Infect Dis 2015;15:671-82.
  4. Henao-Restrepo AM, Longini IM, Egger M, et al. Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial. Lancet 2015.
  5. Flannery B, Clippard J, Zimmerman RK, et al. Early estimates of seasonal influenza vaccine effectiveness - United States, January 2015. MMWR Morb Mortal Wkly Rep 2015;64:10-5.
  6. The Editorial Board. Children Die Because People Are Wrongly Afraid of Vaccines. The New York Times 2015 August 20, 2015.
  7. PPIC Statewide Survey: Californians and Their Government. Public Policy Institute of California, 2015. at http://www.ppic.org/main/publication.asp?i=1153.) 
  8. Mello MM, Studdert DM, Parmet WE. Shifting Vaccination Politics - The End of Personal-Belief Exemptions in California. N Engl J Med 2015.
  9. Horne Z, Powell D, Hummel JE, Holyoak KJ. Countering antivaccination attitudes. Proc Natl Acad Sci U S A 2015;112:10321-4.