Dr. Anthony Flores

Dr. Anthony Flores completed his undergraduate degree at the University of Wyoming.  He received his MD, PhD (Microbiology), and MPH (Epidemiology) from the University of Rochester School of Medicine and Dentistry and moved to Houston, TX in 2006 for his pediatric residency followed by ID fellowship at Baylor College of Medicine and Texas Children’s Hospital.

Currently, Dr. Flores is Associate Professor at McGovern Medical School of the University of Texas Health Sciences Center at Houston.  He is an attending physician in the Division of Pediatric Infectious Diseases at Children’s Memorial Hermann Hospital and MD Anderson Cancer Center in Houston, TX.  In addition, Dr. Flores is a member of the Center for Antimicrobial Resistance and Microbial Genomics where his laboratory studies the epidemiology and molecular pathogenesis of groups A and B streptococci.

Dr. Flores was a former recipient of the Harold Amos Medical Faculty Development Program of the Robert Wood Johnson Foundation and maintains a strong interest in improving diversity in science and medicine. In Dr. Flores’ words, "Improving diversity in our workforce will lead to diversity of thought and ultimately enhance the care we provide to children.”

Kristina Bryant, MD

The Pediatric Infectious Diseases Society is committed to inclusion, diversity, access, and equity (IDA&E) at all levels within the society.  It is critical that the diversity of our membership reflect that of the patients, families, and communities we collectively serve through health care, research, education, and advocacy. We know we have opportunities: a recent report in the Journal of Infectious Diseases on workforce diversity indicated that <20% of the PIDS membership self-reported as underrepresented minorities (Asian, Black/African American, or Hispanic/Latino) and 45% as women (https://academic.oup.com/jid/article/216/suppl_5/S606/4160395).  Using the broader definition of “historically disadvantaged background,” including LGBTQ, socioeconomically disadvantaged, or first-generation college educated to gauge membership diversity, we are not more diverse.

PIDS is recruiting members to join an Inclusion, Diversity, Access, and Equity Task Force. The group’s initial charge will include:

  • Articulate IDA&E principles for our society
  • Review existing policies, practices and processes to identify where we have opportunities to improve and/or implement best practices related to IDA&E
  • Identify strategies to increase under-represented populations among those pursuing careers in pediatric infectious diseases
  • Create a Strategic Roadmap to determine if the identified goals are being met

While this is work that will require broad engagement from society members, we are looking for members to initially serve on the task force. Dr. Anthony Flores has agreed to lead this initiative, with support from Dr. Tina Tan. You can read about Dr. Flores in this month’s member spotlight here.  Dr. Tan is Professor of Pediatrics at the Feinberg School of Medicine, Northwestern University, a pediatric infectious diseases specialist at the Ann & Robert H. Lurie Children’s Hospital of Chicago, and the Chair of the IDSA Diversity, Inclusion and Equity Task Force. 

As you know, PIDS has 6 strategic aims: 

Aim 1: To promote the Value of ID to the healthcare system.

Aim 2: To recruit and train top talent into Pediatric ID Fellowship Programs.

Aim 3: To advance ID science and advocate for support for research in ID.

Aim 4: To engage PIDS membership through innovative programs and services.

Aim 5: To advance clinical care in ID, including appropriate antimicrobial use and childhood vaccinations.

Aim 6: To promote the success of JPIDS. 

I am not proposing to make inclusion, diversity, access, and equity our 7th strategic aim. Rather, our goal is to ensure the principles of IDA&E are inherent in each of our aims, and in all of the activities and interactions internal and external to our society.

Please consider applying for the taskforce here.

Kris 

 

Dear All – 

St Jude and PIDS leadership have made the difficult decision to cancel the upcoming St. Jude/PIDS Conference due to the increasing spread of COVID-19.   This decision was made after several days of deliberation with the conference organizers, PIDS leadership, and the St. Jude Infection Prevention Team.  Out of an abundance of caution, we want to avoid unnecessary exposures to the immunocompromised children of St. Jude; moreover, there is simply no effective way to rapidly screen for the virus and attendees will be travelling from international and national sites, which further confuses risk calculation. 

We know that this decision will affect you all in a number of ways, but we trust that you understand that this is an evolving issue that requires utmost caution. For those who submitted abstracts for presentation, please know that we still plan to publish these in their entirety in an upcoming issue of JPIDS. If you have any other questions or concerns, please feel free to reach out to our PIDS staff at This email address is being protected from spambots. You need JavaScript enabled to view it..

PIDS will continue to update our membership on COVID-19 developments. We wish you all the best as you care for your local communities and advance research on this and other microbes that threaten pediatric health.

Onward and upward,

Elaine and Buddy

Greetings from the PIDS Communications Committee! Our committee oversees and coordinates communications within PIDS, between PIDS and other organizations with shared missions, and between PIDS and the public.  This includes the PIDS website, PIDS Connect, PIDSNews, and social media.  We also evaluate marketing materials, as well as other potential communication vehicles, in meeting the needs of the membership and develop recommendations for future means of communication. This Spring, we will be working with PIDS leadership and staff to develop a new PIDS website to better meet your needs.  Additionally, we will focus our efforts on increasing membership engagement on PIDS Connect, promoting pediatric ID, and PIDS efforts on social media.

If you have questions or suggestions on how our committee can better serve you, please contact Rebecca Wallihan at This email address is being protected from spambots. You need JavaScript enabled to view it.

Thank you,

PIDS Communications Committee

The LEAP Fellowship application deadline has been extended until Monday, February 24th at Midnight Pacific Time.  There is still time to start an application today and this will give those in the process a little more time to complete.

The LEAP Fellowship is a 12 month funded program for early career ID physicians or physicians currently in ID fellowship (MD or DO).  Its purpose is to train ID physicians how to be medical leaders that can bridge the gap between clinical healthcare and public health departments, with a focus on preventing healthcare-associated infections (HAI) and antimicrobial resistance (AR). The program is led by IDSA, SHEA and PIDS, and is funded by the CDC.  This years’ LEAP Fellowship commences July 1, 2020 and carries a $100,000 award for the academic year.

Visit the IDSA website page for more information,  including eligibility      requirements and application materials at www.idsociety.org/LEAPfellowship

 

If you have any questions or concerns, please reach out to Michele Wagner, MPH, LEAP Program Manager, at This email address is being protected from spambots. You need JavaScript enabled to view it. or by phone at 202-462-2618.

I am pleased to share our inaugural Member Spotlight, featuring Sabah Kalyoussef, DO. My hope is that the Member Spotlight will foster connections between PIDS members and highlight the diversity of work that we do as pediatric infection diseases specialists.

Kris

Sabah Kalyoussef, DO

Sabah Kalyoussef, DO is a Volunteer Clinical Assistant Professor at Rutgers-Robert Wood Johnson Medical School. She is an Attending in the Division of Pediatric Infectious Diseases and Division of Hospital Medicine at the Children’s Hospital at Saint Peter’s University Hospital in New Brunswick, NJ.

Dr. Kalyoussef received her undergraduate degree in Biological Sciences from Rutgers, The State University of New Jersey.  She obtained her osteopathic medical degree at Rowan University School of Osteopathic Medicine.  Dr. Kalyoussef then completed her residency at the Children’s Hospital at Saint Peter’s University Hospital and fellowship in Pediatric Infectious Diseases at the Children’s Hospital at Montefiore.  Her research interests include latent tuberculosis infection and pediatric sepsis.

As a part-time pediatric hospitalist, Dr. Kalyoussef has a strong interest in family-centered rounds, resident education and performance improvement projects.  Dr. Kalyoussef serves on the PIDS Education Committee.

Dr. Kalyoussef's own words about why she loves pediatric ID:

"I enjoy being a detective assigned to solve a mystery. ID processes can affect every organ system and require working with residents and staff to help my patients feel better!"

The Surviving Sepsis Campaign, an international group dedicated to improving prevention and treatment of sepsis, has now released its first international guideline specifically for management of sepsis and septic shock in children.

https://link.springer.com/article/10.1007/s00134-019-05878-6

This guideline represents contributions from 49 experts in infectious diseases, critical care, emergency medicine, evidence-based medicine and guideline methodology, as well as community representatives. The Pediatric Infectious Diseases Society provided a representative to the group who provided the perspective and expertise of pediatric infectious disease clinicians, and a focus on the importance of antimicrobial stewardship.

Infectious diseases expertise has been included in many recommendations, including considerations regarding choice of initial antibiotic therapy, identification of appropriate duration of therapy, importance of source control, and the relative importance of timely antibiotics in patients presenting with suspected sepsis. One novel recommendation is to permit a delay in administration of antibiotics for up to 3 hours for expeditious evaluation and diagnosis in patients with suspected sepsis but without shock.

The importance of antimicrobial stewardship has been emphasized throughout the guidelines, including in recommendations to evaluate the effect of sepsis-screening programs on inappropriate antibiotic administration, to perform expeditious evaluation of patients with suspected sepsis to allow responsible antibiotic use, choosing appropriately broad initial antimicrobial therapy, and identifying opportunities for discontinuation or targeting antibiotic therapy.

The Pediatric Infectious Diseases Society is proud to endorse these guidelines, which will improve the care of children with sepsis or septic shock around the world.

Wuhan virus

The Centers for Disease Control and Prevention (CDC) is closely monitoring an outbreak caused by a novel (new) coronavirus first identified in Wuhan, Hubei Province, China. Chinese authorities identified the new coronavirus, which has resulted in hundreds of confirmed cases in China, including cases outside Wuhan, with additional cases being identified in a growing number of countries internationally. The first case in the United States was announced on January 21, 2020. There are ongoing investigations to learn more.

Title: Fidaxomicin use for Clostridioides difficile in pediatrics: Is it all SUNSHINE and roses?   

Reviewing: Wolf J, Kalocsai K, Fortuny C, et al. Safety and efficacy of fidaxomicin and vancomycin in children and adolescents with Clostridioides (Clostridium) difficile infection: a phase 3, multicenter, randomized, single-blind clinical trial (SUNSHINE). Clin Infect Dis. 2019.

Author:                 Shaina Hecht, MD, Fellow, Infectious Diseases, Nationwide Children's Hospital Reviewers:                Sandra Arnold MD, MSc

Amanda Green MD

Background:

There is evidence that the incidence of Clostridioides difficile (CD, formerly Clostridium difficile) infection (CDI) in pediatrics is increasing, and has been associated with increased length of stay and increased risk of mortality in hospitalized children.  Although the majority of initial pediatric CDI cases are successfully treated, up to 40% of cases result in recurrence.  Fidaxomicin, a macrocyclic antibiotic, has been shown to be non-inferior to vancomycin for initial cure of CDI in adults, and significantly reduces the risk of recurrence.  A phase 2a pediatric study, published in 2018, showed a clinical response rate at end of treatment of 92% and a recurrence rate of 31% within 28 days after the end of treatment.  In the current study, the safety and efficacy of fidaxomicin compared to vancomycin was evaluated in pediatrics.

Methods and Results:

This study was a multicenter, investigator-blind, phase 3 trial that prospectively enrolled pediatric patients with non-severe CDI, and randomized patients to treatment with either fidaxomicin or oral vancomycin (2:1).  Diagnosis required diarrhea plus detection of toxin A/B or toxigenic CD in stool using at least one local diagnostic test.  One hundred forty-two patients (of 148 randomized), many of whom had at least one comorbidity, received treatment as allocated, and were followed for safety and efficacy until 30 days after the end of therapy (EOT).

The proportion of patients with confirmed clinical response (defined as clinical response at EOT, with no further requirement for CDI therapy at 2 days after EOT) was similar between patients in the fidaxomicin group and the vancomycin group.  However, there was a significantly higher incidence of recurrence in patients who received vancomycin compared to those who received fidaxomicin (29% versus 12%, respectively) resulting in greater global cure (no relapse within 30 days) with fidaxomicin (68.4%, 67/98) versus vancomycin (50.0%, 22/44) (adjusted treatment difference 18.8%; 95% CI 1.5%, 35.3%).  While not significant, the rate of global cure was higher in immunocompromised patients treated with fidaxomicin.  No serious adverse events were attributed to study treatments.

Critique:

This multicenter, randomized study showed a significantly higher global cure rate in patients treated with fidaxomicin compared to those treated with vancomycin.  Important limitations include enrollment of children < 2 years of age who are more likely to be asymptomatic carriers of toxigenic CD.  Additionally, diagnosis of CDI included PCR and ELISA- based testing, both of which can be positive in asymptomatic carriers.  Despite these concerns, fidaxomicin appears to be a safe and effective treatment option for children with CDI.

Conclusions:

While the study included children who may not have had true CDI, this study supports the safety and efficacy of fidaxomicin use in children and demonstrated a significantly higher cure rate at 30 days in non-severe CDI treated with fidaxomicin.  While the number needed to treat was low (5.3), given the high cost, fidaxomicin will likely be reserved for treatment of patients with a high risk of CDI recurrence, including those with cancer and other serious comorbidities.   Although not statistically significant, the finding of a higher rate of global cure in immunocompromised patients treated with fidaxomicin is promising, suggesting further studies are needed in this patient population. 

Share your thoughts about this review on our PIDS Connect community forum!

References:

  1. Wolf J, Kalocsai K, Fortuny C, et al. Safety and efficacy of fidaxomicin and vancomycin in children and adolescents with Clostridioides (Clostridium) difficile infection: a phase 3, multicenter, randomized, single-blind clinical trial (SUNSHINE). Clin Infect Dis. 2019.

Summary

This health advisory notifies clinicians that influenza activity remains high in the United States. Ongoing elevated activity is due to influenza B/Victoria viruses, increasing circulation of influenza A(H1N1)pdm09 viruses, and low levels of influenza B/Yamagata and influenza A(H3N2) viruses. CDC’s influenza forecasts suggest that national influenza activity will remain elevated for several more weeks. Because influenza activity is elevated and both influenza A and B virus infections can cause severe disease and death, this health advisory also serves as a reminder that early treatment with antiviral medications improves outcomes in patients with influenza. Early treatment with antiviral medications is recommended for hospitalized patients and high-risk outpatients, including children younger than two years. Clinicians should continue efforts to vaccinate patients for as long as influenza viruses are circulating, and promptly start antiviral treatment of severely ill and high-risk patients with suspected influenza without waiting for laboratory confirmation.

Recommendations for Clinicians

1)  All People Six Months and Older Who Have Not Yet Received an Influenza Vaccine this Season Should Be Vaccinated Against Influenza. 

All available vaccine formulations this season contain A(H3N2), A(H1N1)pdm09, and B/Victoria virus strains.21 The 2019-2020 U.S. quadrivalent influenza vaccines contain these and an additional influenza B/Yamagata virus. CDC does not recommend one influenza vaccine formulation over another.

2)  All Hospitalized, Severely Ill, and High-Risk Patients with Suspected or Confirmed Influenza, Regardless of Influenza Vaccination Status, Should Be Treated with Antivirals As Soon As Possible After Onset of Illness Antiviral treatment is recommended as early as possible for any patient with suspected or confirmed influenza who—

  1. Is hospitalized. 
  2. Has severe, complicated, or progressive illness. This may include outpatients with severe or prolonged progressive symptoms or patients who develop complications such as pneumonia but who are not hospitalized.
  3. Is at high risk for influenza complications but not hospitalized. This includes—
  4. Children younger than two years. Although children younger than five years are considered at higher risk for complications from influenza, the highest risk is for those younger than two years.
  5. Adults 65 years and older.
  6. People with chronic pulmonary (including asthma), cardiovascular (except hypertension alone), renal, hepatic, hematological (including sickle cell disease), and metabolic (including diabetes mellitus) disorders.
  7. People with neurologic and neurodevelopment conditions, including disorders of the brain, spinal cord, peripheral nerve, and muscle, such as cerebral palsy, seizure disorder, stroke, intellectual disability, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury.
  8. People with immunosuppression, including that caused by medications or by HIV infection.
  9. Women who are pregnant or postpartum (within two weeks after delivery).
  10. People younger than 19 years who are receiving long-term aspirin therapy.
  11. American Indians and Alaska Natives.
  12. People with extreme obesity (i.e., body mass index is equal to or greater than 40).
  13. Residents of nursing homes and other chronic care facilities.

3)  Antiviral Treatment in Non-High-Risk Patients with Uncomplicated Influenza


Antiviral treatment can benefit other individuals with influenza. While current guidance focuses on antiviral treatment of those with severe illness or at high risk of complications, antiviral treatment may be prescribed for any previously healthy (non-high risk) outpatient with suspected or confirmed influenza who presents within two days after illness onset. Multiple randomized controlled clinical trials (RCTs) and meta-analyses of RCTs have demonstrated efficacy of early initiation of treatment (started within 48 hours of illness onset) with neuraminidase inhibitors in reducing duration of fever and illness symptoms by about a day compared with placebo in otherwise healthy children and adults with uncomplicated influenza.6,9 Clinical judgment—considering the patient’s disease severity and progression, age, likelihood of influenza, and time since onset of symptoms is important when making antiviral treatment decisions for outpatients who are not at increased risk for influenza complications.

4)  Choice of Antiviral Medication


Four influenza antiviral medications approved by the U.S. Food and Drug Administration (FDA) are recommended for use in the United States during the 2019-2020 influenza season.  Three drugs are chemically related antiviral medications known as neuraminidase inhibitors: oral oseltamivir phosphate (available as a generic version or under the trade name Tamiflu®), inhaled zanamivir (trade name Relenza®), and intravenous peramivir (trade name Rapivab®). These medications block the viral neuraminidase enzyme and have activity against both influenza A and B viruses.

View this advisory in its entirety here:  CDC Advisory

Download the IDSA Flu Practice Guidelines

REQUEST FOR APPLICATIONS

Ralph D Feigin, MD, UpToDate® Pediatric Subscription Awards

Background

UpToDate®, in conjunction with Texas Children’s Hospital, has established a series of pediatric subscription awards in honor of Dr Ralph David Feigin, who had been Editor-In-Chief of the Pediatrics Section of UpToDate since its inception in 1999.  The award grants up to six, three-year subscriptions to UpToDate®  to physicians, other health care providers, or health care facilities that provide care to underserved or low-income children and who could not otherwise afford the subscription.  The deadline for applications is May 31. Awardees will be announced in June, and the subscriptions will start in July, 2020.

Criteria

Applicants must meet all four (A, B, C, and D) of the following qualifications. 

  1. Practice or teach in low-income or medically underserved areas.

A low-income or medically underserved area is defined as meeting any one of the following:

      1) a rural area more than 50 miles from the nearest city with a population of 400,000 or more and more than 50 miles from a medical school

      2) a practice in which 50% or more of the patients are uninsured, are insured by a governmental program or are identified as minorities

      3) a community or area designated by a governmental agency or governmental representative as medically underserved or qualifies as a health professional shortage area

      4) a low-income country as designated by the WHO 

Deliver health care or health education to children and their families

Do not currently have access to UpToDate® and are unable to afford the initial one-year subscription of approximately $500 and the approximately $400 yearly renewal fee.

Have access to a computer with internet capability.

Application Process

Applicants should complete the application below electronically and submit as a word document.  Cells may be expanded as needed.

Completed applications (as a word document) should be submitted to Martin I Lorin, MD (This email address is being protected from spambots. You need JavaScript enabled to view it.) by May 31, 2020. (Application

 

PIDS Journal Club, December 2019

 

Immune Monitoring of CMV After Transplantation? Refinements in Our Approach Are Necessary.

Reviewing: Paouri B et. al., “Quantiferon-Cytomegalovirus Assay: A Potentially Useful Tool in the Evaluation of CMV-Specific CD8+ T-Cell Reconstitution in Pediatric Hematopoietic Stem Cell Transplant Patients”, Ped. Transplant., 20181

Background

Despite improvements in the detection and management of cytomegalovirus (CMV), morbidity and mortality remain significant in the transplant population. Methods that might improve risk stratification, that might reduce drug toxicity and that might reduce levels of drug resistance are necessary to improve management. Reconstitution of CMV specific immunity in hematopoietic stem cell transplant (HSCT) patients has been associated with control of and protection against CMV reactivation and disease. In this paper, the investigators evaluated the clinical utility of using CMV specific cell mediated immune responses to predict CMV DNAemia in pediatric HSCT patients. 

Methods and Results

Thirty-seven pediatric HSCT patients were followed prospectively. Weekly CMV PCR was performed to look for DNAemia until day 100 and then if clinically indicated. The Quantiferon-CMV assay was performed prior to transplant, early after transplant and at days 30, 90, 180, 270, and 360 after transplant.

The principle behind the Quantiferon-CMV is identical to the Quantiferon-TB. Whole blood is placed in separate tubes with a negative control, a mitogen positive control, and specific CD8 stimulating peptides. After incubation, interferon gamma is measured and can be reported as qualitatively positive, negative, or indeterminate or as a quantitative result. Production of interferon gamma acts as a surrogate for stimulation of CD8 specific T cells, in this case, to CMV.

Prior to transplant, 17 (46%) patients were negative by Quantiferon-CMV, 12 (32%) patients were indeterminate, and 5 (14%) were positive. There was no correlation between pre-transplant cell mediated immunity (CMI) and CMV DNAemia at < 30 days post-transplant. CMV DNAemia occurred in 51% of patients with half of those episodes occurring at < 30 days presumably before full engraftment. Fifteen of these DNAemic patients (40% of total cohort) developed immunity at an average of 82 days’ post-transplant. In those who developed immunity, later reactivation of CMV was lower (15% vs. 53%) than in those who did not develop immunity. In this cohort, acute graft versus host disease (GVHD) did not alter the recovery of CMV immunity.

Critique

The percentage of indeterminate results was high in this cohort and may reflect disease state or conditioning regimen for transplant, as over 50% of the indeterminate samples were drawn in the 1-3 days after transplant. In addition, this method is probably not helpful in the early post-transplant period at least for those with an HSCT. It should, however, be more useful in those receiving a solid organ transplant (SOT) as pre-existing immunity remains after conditioning. The technique appears to have merit and may be useful in the future once larger prospective studies are undertaken.

Conclusions 

Immune monitoring of CMV may help with stratifying patients for episodes of reactivation, as those who recovered CMV immunity were less likely to reactivate in this cohort. However, since most episodes of CMV reactivation occurred before immune reconstitution was expected, the clinical utility of this assay may be limited in HSCT patients to post engraftment. However, CMV immunity prior to transplant in those receiving a SOT, may also predict who will be more likely to control DNAemia. A prospective trial is underway in adult patients (NCT02538172) 2

Share your thoughts about this review on our PIDS Connect community forum!

Author

Marc Foca, MD

Columbia University Irving Medical Center, New York, NY USA

Peer Reviewers

Joshua Wolf MBBS, PhD, FPIDS, FRACP, St. Jude Children’s Research Hospital, Memphis, TN

Sanjeev Swami MD, The Children’s Hospital of Philadelphia, Philadelphia, PA

References 

  1. PaouriB, Soldatou A, Petrakou E, Theodosaki M, Tsentidis C, Kaisari K, Oikonomopoulou C, Matsas M, Goussetis E. Quantiferon-Cytomegalovirus assay: A potentially useful tool in the evaluation of CMV-specific CD8+ T-cell reconstitution in pediatric hematopoietic stem cell transplant patients. Pediatr Transplant. 2018 Aug;22(5):e13220. doi: 10.1111/petr.13220. Epub 2018 May 18. 
  1. Clinical Trials.gov. Cell Mediated Immunity for Prevention of CMV Disease.

https://clinicaltrials.gov/ct2/show/NCT02538172. Sept. 2015. Accessed Dec. 2019

Journal of the Pediatric Infectious Diseases Society

NEWS RELEASE

Influenza can be especially dangerous for children, who are at greater risk for serious complications from the illness, including hospitalization and even death. Yet child care centers in the U.S. rarely require children or the adults who care for them to be vaccinated against flu, according to a new study published in the Journal of the Pediatric Infectious Diseases Society.

At the United Nations General Assembly meeting in New York City on September 23, 2019, the Center for Disease Control hosted the Antimicrobial Resistance Challenge: A night celebrating antimicrobial resistance fighters. The venue brought together representatives from various organizations and institutions engaged in the fight against antimicrobial resistance, including PIDS, and showcased artwork bringing attention to the fight against antimicrobial resistance. The event premiered the film “Antimicrobial Resistance Fighters,” which was directed by Michael Wech and introduced by Dame Sally Davies, the Chief Medical Officer for England and Chief Medical Advisor to the UK government.

This powerful and well-made documentary highlighted individual stories to explain the threat of antimicrobial resistance to the general public. One such story featured Mr. David Ricci, a white American young man who spoke passionately at the event about his journey combating an infection that he contracted while living in Calcultta, India. In 2011, Mr. Ricci worked as a volunteer at an orphanage for children living with HIV/AIDS, when he barely survived a horrific accident in which he was struck by a train, his bones and muscles crushed as he was dragged under. The film showed footage of the location where the accident took place, alongside piles of waste and trash where volunteers pulled him out from under the train. At a local clinic his leg was sawed off above the knee at the bedside without anesthesia. He was transferred to a hospital where he underwent multiple surgeries. Brief footage in the film flashed images of his initial wound against the backdrop of the grounds of his accident.  Mr. Ricci flew back home to the U.S. two weeks after the accident where he was cared for at the University of Washington Medical Center in Seattle. He was found to have a wound infection caused by multiple bacteria that harbored the New Delhi metallobetalactamse-1 enzyme. Dr. John Lynch, the infectious diseases physician caring for him at the University of Washington, explained that after several antibiotics failed, they ultimately treated Mr. Ricci’s infection with colistin and a series of surgical debridements.

Mr. Ricci, who is now a patient advocate and antimicrobial resistance fighter, described his body’s reaction to each dose of colistin as feeling like his organs were being eaten away. Later in the film, another story unfolds describing the use of colistin in agriculture. Mr. Ricci comments that despite the toxic effects that colistin had on his body, the effectiveness of this last line drug against his multi-drug resistant infection saved his life. He acknowledges that he is alive because the bacteria causing his infection were still susceptible to colistin. He expresses his astonishment that our society could allow widespread agricultural use of colistin that would threaten its effectiveness.

 “Antimicrobial Resistance Fighters” was powerful, and will raise awareness to the general public about the global threat of antimicrobial resistance. The film is an example of what events like the AMR Challenge strives to accomplish by bringing together advocates in the fight against antimicrobial resistance from all disciplines, reminding us that we must work together to share our experiences and expertise. 

By Rana Hamdy; Newsletter Edition 9.23.19

To learn more about PIDS AMR efforts, visit our Antibiotic Resistance page here.  U.S. Antibiotic Awareness Week is being observed November 18-24, 2019.

Dropulic LK,  et.al.  A Randomized, Double-Blinded, Placebo-Controlled, Phase 1 Study of a Replication-Defective Herpes Simplex Virus (HSV) Type 2 Vaccine, HSV529, in Adults With or Without HSV Infection. J Infect Dis 2019;220:990.

 

Background

Both genital and oral herpes simplex virus (HSV) infections are common throughout the world.  Most infections are asymptomatic but many produce painful ulcerations that often recur.  Further, neonatal HSV infections produce a severe disease while genital HSV-2 infections are a major risk factor for the acquisition and transmission of HIV.

Methods and results

In this manuscript the authors describe the initial clinical evaluation of a replication defective herpes simplex virus vaccine.  A replication defective vaccine is one in which one or more essential genes have been deleted so the vaccine virus, which is grown in a cell line that provides the missing gene product(s),  can infect a cell but the virus produced is non-infectious because of the deletions.  Thus, another term used is a single cycle vaccine.  This is one of several new approaches to vaccine development discussed briefly below.

The vaccine HSV529 (HSV-2 dl5-29), a double deletion of  HSV-2 UL5 and UL 29, was evaluated in 60 healthy adults in a double blind study of participants who were either seronegative for HSV1 and HSV-2, or positive for either HSV-1 or HSV-2 or both.  The vaccine was provided in a 3 dose schedule administered IM at 0,1 and 6 months. Safety and both antibody and T cell responses were quantified.

The overall safety profile of the vaccine was acceptable although mild to moderate local reactions were common (89%).  There was no significant difference compared to placebo recipients in unsolicited adverse events.  A fourfold increase in neutralizing antibody titers was induced in 11 of 14 HSV seronegative participants after the third dose and titers remained elevated at 6 months. For those HSV seropositive, there was a mixed response but none of the recipients had a 4 fold increase.  There was also some evidence of T cell induction but CD8 responses were weak in seronegative participants and were even less for seropositive subjects.  CD4 responses were higher than CD8 for both groups.

Discussion

This is an interesting time for HSV vaccines.  The recent failure of a prophylactic (to prevent disease and persistent infection) monovalent glycoprotein D (gD) vaccine to protect against HSV-2 (1) and the sub optimal but significant decrease in recurrent HSV-2 disease and shedding by a bivalent therapeutic vaccine (to decrease recurrent disease and shedding in those already infected) (2) has led many to believe that a successful vaccine must present more HSV antigens.  Hence the development of this replication defective candidate as well as live attenuated vaccines that have deleted neuroinvasive HSV proteins (3,4) in order to present more HSV antigens.  On the positive side the prophylactic gD2 candidate did protect against HSV-1 genital disease and infection (1) and established a correlate of protection (5) providing encouragement to the field.  Similarly, the therapeutic vaccine established a proof of concept for therapeutic vaccines.  The vaccine evaluated in the current manuscript offers advantages to the subunit vaccines evaluated previously, in that it presents all the HSV antigens to the immune system.  However, it remains unclear as to whether a single round of virus replication will be sufficient to induce long lasting protection.  Also of interest, similar approaches have recently been used for cytomegalovirus (CMV) vaccines after the partial success of a monovalent glycoprotein B CMV vaccine (6).  Thus both replication defective (7) and live attenuated vaccines (8) are being developed.

Stay tuned for results of upcoming clinical trials for these and other herpes virus vaccines.

Share your thoughts about this review on our PIDS Connect community forum!

References

  1. Belshe RB, Leone PA, Bernstein DI, et.al. Herpevac Trial for Women. Efficacy results of a trial of a herpes simplex vaccine. N Engl J Med. 366:34; 2012.
  2. Bernstein DI, Flechtner JB, McNeil et.al. Therapeutic HSV-2 vaccine decreases recurrent virus shedding and recurrent genital herpes disease. Vaccine.  37:3443; 2019.
  3. Bernstein DI, Pullum DA, Cardin RD, et.al.  The HSV-1 live attenuated VC2 vaccine provides protection against HSV-2 genital infection in the guinea pig model of genital herpes. Vaccine. 37:61; 2018
  4. Richards AL, Sollars PJ, Pitts JD, et.al.  The pUL37 tegument protein guides alpha-herpesvirus retrograde axonal transport to promote neuroinvasion. PLoS Pathog. 13: e1006741; 2017.
  5. Belshe RB, Heineman TC, Bernstein DI, et.al. Correlate of immune protection against HSV-1 genital disease in vaccinated women. J Infect Dis. 209:828; 2014.
  6. Bernstein DI, Munoz FM, Callahan ST, et. al.  Safety and efficacy of a cytomegalovirus glycoprotein B (gB) vaccine in adolescent girls: A randomized clinical trial. Vaccine.34:313; 2016
  7. Adler SP, Lewis N, Conlon A, et.al.  Clinical Trial of a Conditionally Replication-Defective Human Cytomegalovirus (CMV) Vaccine in CMV-Seronegative Subjects. J Infect Dis. 220:411; 2019
  8. Hansen SG, Marshall EE, Malouli D, et.al. A live-attenuated RhCMV/SIV vaccine shows long-term efficacy against heterologous SIV challenge. Sci Transl Med. Jul 17;11; 2019.

Author

David Bernstein MD (Cincinnati Children’s Hospital Medical Center)

Peer Reviewers

Sandra L Arnold MD (Le Bonheur Children’s Medical Center)

Christine Salvatore MD (Komansky Children's Hospital)

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