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bacteriophage

Phage therapy draws renewed interest to combat drug-resistant microbes

bacteriophage

In the face of growing antibiotic resistance and few antibiotics in the development pipeline, phages are drawing renewed research interest as a potential silver bullet.

The married professors were spending their Thanksgiving holiday in Egypt when the husband, Thomas L. Patterson, Ph.D., got very sick very quickly, experiencing fever, nausea and a racing heartbeat. By the time Patterson was accurately diagnosed with a highly multi-drug resistant bacterial infection, he was near death. His wife, Steffanie Strathdee, Ph.D., promised to “leave no stone unturned.’”

What happened next is the ultimate infectious disease feel good story: Strathdee, part of an All-Star team of infectious disease experts and epidemiologists, concocted a cocktail of viruses that killed the superbug and saved Patterson’s life.

“He was going to die,” says Roberta L. DeBiasi, M.D., MS, chief of the Division of Pediatric Infectious Diseases at Children’s National Health System. “Because of her epidemiology background – and because she loves him – Patterson became the first patient successfully treated with bacteriophages.”

Dr. DeBiasi explains that all viruses take over cells and use their machinery for their own purposes. In order to escape, viruses blow up the cell. Bacteriophages are viruses that target bacteria, taking over their machinery and ultimately killing the bacterial host.

“Infection is a race between the body’s immune response and the bacteria replicating themselves,” she adds. “Bacteria have to continually replicate. If you knock out 90 percent of them with phage therapy, that gives the immune system a fighting chance to win the race.”

She was so inspired by the team’s ingenuity that DeBiasi, program vice-chair, invited them to recount the story during IDWeek2018, held Oct. 3 to Oct. 7, 2018, in San Francisco. During the closing plenary, Patterson, a professor of psychiatry, and Strathdee, associate dean of Global Health Sciences, will be joined by Robert T. “Chip” Schooley, M.D., (all of University of California, San Diego), to discuss the clinical aspects and efficacy of phage therapy.

About 50 years ago, the U.S. military had investigated leveraging phages but ultimately placed that research portfolio on the back burner. Now, in the face of growing antibiotic resistance and few experimental antibiotics in the development pipeline, phages are drawing renewed research interest as a potential silver bullet.

“The technology has been around for 50 years. We’re going back to old things because we’re so desperate,” Dr. DeBiasi adds.

The tricky thing with phages is that each bacterium needs its own tailored phage therapy.

Children’s National is working with Adaptive Phage Therapeutics, a company based in Gaithersburg, Maryland, that developed the phage used to save Patterson, in order to help build out that library of phages, each ready to be directed to do battle against a specific pathogen.

“We have been consultants to them to think about what would be a good clinical trial, particularly in a pediatric population,” Dr. DeBiasi says.

Children’s National has been collecting and sending isolates from patients with neurogenic bladder who experience urinary tract infections to shore up the phage library in anticipation of a clinical trial. The work builds on Children’s experience as the first center to use phage therapy in a pediatric patient, a 2-year-old who had multidrug-resistant Pseudomonas aeruginosa infection complicated by bacteremia/sepsis.

drawing of neurons

Children’s National to host 28th Annual Pediatric Neurology Update

drawing of neurons

The Children’s National Health System Center for Neuroscience and Behavioral Medicine is proud to host the 28th Annual Pediatric Neurology Update course.

This year’s course will be focused on new understandings, molecular pathogenesis, novel treatment and outcomes of infections which affect the central nervous system; as well as the often indistinct boundaries between CNS infections and neuro immunologic diseases of the nervous system.

We invite you to join us for presentations from renowned experts in the field in this full-day, CME accredited event on May 3, 2018 at the Children’s National main campus in Washington, D.C.

For more information and to register, visit ChildrensNational.org/NeurologyUpdate.

Roberta DeBiasi and Sarah Mulkey

Children’s National experts contribute to new Zika guidelines

Roberta DeBiasi and Sarah Mulkey

Roberta DeBiasi, M.D., M. S., and Sarah B. Mulkey, M.D., Ph.D., members of Children’s multidisciplinary Congenital Zika Virus Program, were among the experts invited to participate in a forum held in Atlanta at CDC headquarters in late August to formulate new Zika recommendations.

The Centers for Disease Control and Prevention (CDC) on Oct. 19, 2017 updated guidelines for evaluation of women, fetuses and infants exposed to the Zika virus during pregnancy. Although only women with symptoms will now be routinely tested, asymptomatic and symptomatic infants born to these women will still be tested for the Zika virus using blood and urine tests.

Infants who appear normal, whose mothers either had negative Zika results or who had not undergone testing, will not undergo Zika testing. These infants still will undergo a standard evaluation, including a detailed physical exam, hearing screen and routine developmental assessments. The revised Zika guidance includes input from practitioners on the front lines of the Zika epidemic, including Children’s National Health System clinicians.

“These changes in the recommendations for Zika testing should not be interpreted as Zika infection risks subsiding for pregnant women and their infants in the United States. It’s simply an acknowledgement of the limitations of current testing methods – which must occur within a narrow window after Zika exposure – and the poor predictive value of Zika testing right now,” says Roberta L. DeBiasi, M.D., M.S., chief of Children’s Division of Pediatric Infectious Diseases. Dr. DeBiasi and Sarah B. Mulkey, M.D., Ph.D., members of Children’s multidisciplinary Congenital Zika Virus Program, were among the experts invited to participate in the Zika forum held in Atlanta at CDC headquarters in late August to formulate the recommendations.

While all infants will receive a standard evaluation, expanded evaluations that include an ophthalmologic assessment, more detailed hearing evaluation and ultrasound of the newborn’s head will be reserved for infants born to mothers confirmed to be Zika positive or Zika probable, or for infants born with abnormalities potentially consistent with congenital Zika syndrome, regardless of maternal status.

The majority of U.S. infants who have been exposed to Zika in the womb appeared normal at birth, according to CDC registries. Now, the next wave of these normal-appearing babies will receive standard evaluations when they are born, including a newborn hearing screening. At each well-child visit, these infants will receive:

  • A comprehensive physical examination
  • An age-appropriate vision screening
  • Developmental monitoring and screening using validated tools

“This is a natural evolution in the diagnosis and screening strategy now that the peak of the first wave of Zika transmission appears to be over,” Dr. DeBiasi says. “While we continue to evaluate new possible cases of Zika infection among pregnant women in our practice, a sizable proportion of Children’s cases are Zika-exposed infants whose physical exam and neuroimaging appeared normal at birth. Through ongoing monitoring, we hope to learn more about these children’s long-term neurodevelopment outcomes.”

Children’s National expert joins a national discussion on Zika and other emerging threats

Roberta DeBiasi

“Our goal is to provide the earliest and most accurate information to women affected by Zika exposure and infection during pregnancy, including capability for fetal MRI,” says Roberta DeBiasi, M.D., M.S., chief of the Division of Pediatric Infectious Diseases and co-director of the Congenital Zika Virus Program at Children’s National Health System.

An expert roundtable discussion, “Facing the Zika Crisis and Other Emerging Threats,” organized in collaboration with Purdue University, the Gallup Organization and the Bipartisan Policy Center, was recently held at the U.S. Capitol. Chief of the Division of Pediatric Infectious Diseases and Co-Director of the Congenital Zika Program at Children’s National Health System, Roberta DeBiasi, M.D.,M.S., weighed in on the discussion, sharing knowledge on the challenges to the United States health system and the continuous research and work that the Children’s National Congenital Zika program does.

Eighteen months ago, Children’s National received its first referral for a Washington, D.C. woman who had a Zika infected pregnancy in January 2016. This case prompted the development of the Congenital Zika program to serve as a consultation resource for affected women and infants, and to perform research to address the knowledge gaps concerning Zika infection during pregnancy: Young researchers tackle Zika’s unanswered questions.

“Our goal is to provide the earliest and most accurate information to women affected by Zika exposure and infection during pregnancy, including capability for fetal MRI,” says Dr. DeBiasi.

Since then, the Zika team has evaluated 65 mother-fetus/infant pairs. Researchers are actively learning the best methods for detection of infection and neurologic injury by continually conducting research and obtaining new and useful information that can be shared with others. The research mission of the Congenital Zika program is now focusing on several areas, which include the study of biomarkers to predict if the infant could be affected by the disease, the utility of a fetal MRI in conjunction with ultrasound, genetic risk factors in mothers and infants that might explain why some infants become infected and some do not, long term neurodevelopment of babies that are infected, and neuropathologic evaluations of brains from fetuses that have died from Zika.

The challenges and concerns that were presented for the United States health system include the willingness and ability to share information, the acceptance of the need for data sharing between institutions and determining if testing resources are adequate and appropriate.

Dr. DeBiasi says, “Institutions have become much better at looking at how to prepare for emerging infectious diseases on a broader level.” Proactively thinking, Dr. DeBiasi finds it useful for health systems to use their own task forces, such as the Ebola Response Task force at Children’s National, as a cohesive existing team that will be prepared for additional infectious disease threats that may arise.