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FDA approves Duchenne muscular dystrophy treatment under ‘accelerated pathway’
The first treatment for Duchenne muscular dystrophy has been greenlighted by the Food and Drug Administration.
The injectable eteplirsen (Exondys 51) was approved under the accelerated approval pathway, designed to fast-track medicines thought to exceed the benefits of existing treatments for life-threatening diseases, and was also granted priority review and an orphan drug designation. Eteplirsen is specifically indicated for patients who have a confirmed mutation of the dystrophin gene predisposed to exon 51 skipping. This includes about 13% of the population with Duchenne muscular dystrophy, which occurs in about 1 of every 3,600 male infants worldwide.
“In rare diseases, new drug development is especially challenging due to the small numbers of people affected by each disease and the lack of medical understanding of many disorders,” Janet Woodcock, MD, the FDA’s director of the Center for Drug Evaluation and Research (CDER), said in a statement.
The FDA found that data submitted by Sarepta Therapeutics sufficiently demonstrated an increase in dystrophin production, raising the possibility that there may be clinical benefit in this patient cohort; however, because eteplirsen’s actual clinical benefit has not been established, the FDA is requiring Sarepta to conduct a clinical trial. The study will assess whether eteplirsen improves motor function of this patient population. If the trial fails, the FDA is likely to withdraw approval.
“Accelerated approval makes this drug available to patients based on initial data, but we eagerly await learning more about the efficacy of this drug through a confirmatory clinical trial,” Dr. Woodcock said.
The accelerated approval of eteplirsen is based on the surrogate endpoint of dystrophin increase in skeletal muscle observed in some patients given a trial of the drug. The drug’s tentative labeling shows that in a small, randomized trial, three of eight boys who received either 30 mg/kg or 50 mg/kg per week of eteplirsen experienced balance disorder and vomiting. Contact dermatitis also was reported in two of the boys treated with eteplirsen. None of these adverse reactions were reported in four boys who received placebo.
In subsequent studies of 88 boys given either 30 mg/kg or 50 mg/kg per week of eteplirsen for up to 208 weeks, adverse reactions were reported at rates of 10% or higher, including vomiting, contusion, excoriation, arthralgia, rash, catheter site pain, and upper respiratory tract infection.
Priority review status is granted to an investigational drug based on its potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan drug designation provides incentives such as clinical trial tax credits, user fee waiver, and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.
In a letter to CDER staff, Dr. Woodcock said that “The approval of Exondys 51 reflects FDA’s ability to apply flexibility to address challenges we often see with rare, life-threatening diseases – while remaining within our statutory framework. In this case, flexibility is warranted because of the life-threatening nature of the disease; the lack of available therapy; the fact that the intended population is a small subset of an already rare disease; and the fact that this is a life-limiting disease of children. These factors, combined with the dystrophin production data – and the drug’s low risk profile – led the Agency to approve the drug under the accelerated approval pathway.”
Dr. Woodcock noted that in April 2016, members of an advisory committee recommended that there was not substantial evidence that the drug is effective in providing clinical benefit and also voted 7-6 against accelerated approval because of uncertainties about the dystrophin data presented by the sponsor. But Sarepta later submitted additional data showing substantial evidence of dystrophin production, although the amount of dystrophin produced was only a small fraction of the normal level, she said.
On Twitter @whitneymcknight
The first treatment for Duchenne muscular dystrophy has been greenlighted by the Food and Drug Administration.
The injectable eteplirsen (Exondys 51) was approved under the accelerated approval pathway, designed to fast-track medicines thought to exceed the benefits of existing treatments for life-threatening diseases, and was also granted priority review and an orphan drug designation. Eteplirsen is specifically indicated for patients who have a confirmed mutation of the dystrophin gene predisposed to exon 51 skipping. This includes about 13% of the population with Duchenne muscular dystrophy, which occurs in about 1 of every 3,600 male infants worldwide.
“In rare diseases, new drug development is especially challenging due to the small numbers of people affected by each disease and the lack of medical understanding of many disorders,” Janet Woodcock, MD, the FDA’s director of the Center for Drug Evaluation and Research (CDER), said in a statement.
The FDA found that data submitted by Sarepta Therapeutics sufficiently demonstrated an increase in dystrophin production, raising the possibility that there may be clinical benefit in this patient cohort; however, because eteplirsen’s actual clinical benefit has not been established, the FDA is requiring Sarepta to conduct a clinical trial. The study will assess whether eteplirsen improves motor function of this patient population. If the trial fails, the FDA is likely to withdraw approval.
“Accelerated approval makes this drug available to patients based on initial data, but we eagerly await learning more about the efficacy of this drug through a confirmatory clinical trial,” Dr. Woodcock said.
The accelerated approval of eteplirsen is based on the surrogate endpoint of dystrophin increase in skeletal muscle observed in some patients given a trial of the drug. The drug’s tentative labeling shows that in a small, randomized trial, three of eight boys who received either 30 mg/kg or 50 mg/kg per week of eteplirsen experienced balance disorder and vomiting. Contact dermatitis also was reported in two of the boys treated with eteplirsen. None of these adverse reactions were reported in four boys who received placebo.
In subsequent studies of 88 boys given either 30 mg/kg or 50 mg/kg per week of eteplirsen for up to 208 weeks, adverse reactions were reported at rates of 10% or higher, including vomiting, contusion, excoriation, arthralgia, rash, catheter site pain, and upper respiratory tract infection.
Priority review status is granted to an investigational drug based on its potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan drug designation provides incentives such as clinical trial tax credits, user fee waiver, and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.
In a letter to CDER staff, Dr. Woodcock said that “The approval of Exondys 51 reflects FDA’s ability to apply flexibility to address challenges we often see with rare, life-threatening diseases – while remaining within our statutory framework. In this case, flexibility is warranted because of the life-threatening nature of the disease; the lack of available therapy; the fact that the intended population is a small subset of an already rare disease; and the fact that this is a life-limiting disease of children. These factors, combined with the dystrophin production data – and the drug’s low risk profile – led the Agency to approve the drug under the accelerated approval pathway.”
Dr. Woodcock noted that in April 2016, members of an advisory committee recommended that there was not substantial evidence that the drug is effective in providing clinical benefit and also voted 7-6 against accelerated approval because of uncertainties about the dystrophin data presented by the sponsor. But Sarepta later submitted additional data showing substantial evidence of dystrophin production, although the amount of dystrophin produced was only a small fraction of the normal level, she said.
On Twitter @whitneymcknight
The first treatment for Duchenne muscular dystrophy has been greenlighted by the Food and Drug Administration.
The injectable eteplirsen (Exondys 51) was approved under the accelerated approval pathway, designed to fast-track medicines thought to exceed the benefits of existing treatments for life-threatening diseases, and was also granted priority review and an orphan drug designation. Eteplirsen is specifically indicated for patients who have a confirmed mutation of the dystrophin gene predisposed to exon 51 skipping. This includes about 13% of the population with Duchenne muscular dystrophy, which occurs in about 1 of every 3,600 male infants worldwide.
“In rare diseases, new drug development is especially challenging due to the small numbers of people affected by each disease and the lack of medical understanding of many disorders,” Janet Woodcock, MD, the FDA’s director of the Center for Drug Evaluation and Research (CDER), said in a statement.
The FDA found that data submitted by Sarepta Therapeutics sufficiently demonstrated an increase in dystrophin production, raising the possibility that there may be clinical benefit in this patient cohort; however, because eteplirsen’s actual clinical benefit has not been established, the FDA is requiring Sarepta to conduct a clinical trial. The study will assess whether eteplirsen improves motor function of this patient population. If the trial fails, the FDA is likely to withdraw approval.
“Accelerated approval makes this drug available to patients based on initial data, but we eagerly await learning more about the efficacy of this drug through a confirmatory clinical trial,” Dr. Woodcock said.
The accelerated approval of eteplirsen is based on the surrogate endpoint of dystrophin increase in skeletal muscle observed in some patients given a trial of the drug. The drug’s tentative labeling shows that in a small, randomized trial, three of eight boys who received either 30 mg/kg or 50 mg/kg per week of eteplirsen experienced balance disorder and vomiting. Contact dermatitis also was reported in two of the boys treated with eteplirsen. None of these adverse reactions were reported in four boys who received placebo.
In subsequent studies of 88 boys given either 30 mg/kg or 50 mg/kg per week of eteplirsen for up to 208 weeks, adverse reactions were reported at rates of 10% or higher, including vomiting, contusion, excoriation, arthralgia, rash, catheter site pain, and upper respiratory tract infection.
Priority review status is granted to an investigational drug based on its potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan drug designation provides incentives such as clinical trial tax credits, user fee waiver, and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.
In a letter to CDER staff, Dr. Woodcock said that “The approval of Exondys 51 reflects FDA’s ability to apply flexibility to address challenges we often see with rare, life-threatening diseases – while remaining within our statutory framework. In this case, flexibility is warranted because of the life-threatening nature of the disease; the lack of available therapy; the fact that the intended population is a small subset of an already rare disease; and the fact that this is a life-limiting disease of children. These factors, combined with the dystrophin production data – and the drug’s low risk profile – led the Agency to approve the drug under the accelerated approval pathway.”
Dr. Woodcock noted that in April 2016, members of an advisory committee recommended that there was not substantial evidence that the drug is effective in providing clinical benefit and also voted 7-6 against accelerated approval because of uncertainties about the dystrophin data presented by the sponsor. But Sarepta later submitted additional data showing substantial evidence of dystrophin production, although the amount of dystrophin produced was only a small fraction of the normal level, she said.
On Twitter @whitneymcknight
AUDIO: New NIMH director discusses future of depression therapy
NEW YORK – In this first of four interviews, the new director of the National Institute of Mental Health, Joshua A. Gordon, MD, PhD, shares his thoughts about the emerging nosology of depression and whether it might be possible to identify and turn off genetic pathways implicated in depression without impacting creativity, sexual drive, and appetite.
Dr. Gordon is a practicing psychiatrist and a neuroscientist whose primary area of research is in the emerging field of optogenetics, which uses light to trace the genetically predetermined neurocircuitry of various mental states through the brain.
He steps into his leadership role with NIMH at a time when some have voiced concern that the institute has placed too much emphasis on future therapies, instead of on what can be done in the here and now to treat mental disorders.
Also in this series, Dr. Gordon discusses how, under his leadership, NIMH will balance the priorities of clinicians in everyday practice with those of researchers. He also explains the finer points of optogenetics. Currently, the technique is being studied only in mouse models; but if it makes it to human trials, researchers will explore the ability to switch on and off certain mental states.
Dr. Gordon talks about the ethical implications of optogenetics, as well as his belief in the biological basis of all thought and emotion, and how that guides the search for targeted treatments.
Finally, he’ll discuss what he believes NIMH’s top priorities should be, and whether he will blog as did his predecessor, Thomas R. Insel, MD.
On Twitter @whitneymcknight
NEW YORK – In this first of four interviews, the new director of the National Institute of Mental Health, Joshua A. Gordon, MD, PhD, shares his thoughts about the emerging nosology of depression and whether it might be possible to identify and turn off genetic pathways implicated in depression without impacting creativity, sexual drive, and appetite.
Dr. Gordon is a practicing psychiatrist and a neuroscientist whose primary area of research is in the emerging field of optogenetics, which uses light to trace the genetically predetermined neurocircuitry of various mental states through the brain.
He steps into his leadership role with NIMH at a time when some have voiced concern that the institute has placed too much emphasis on future therapies, instead of on what can be done in the here and now to treat mental disorders.
Also in this series, Dr. Gordon discusses how, under his leadership, NIMH will balance the priorities of clinicians in everyday practice with those of researchers. He also explains the finer points of optogenetics. Currently, the technique is being studied only in mouse models; but if it makes it to human trials, researchers will explore the ability to switch on and off certain mental states.
Dr. Gordon talks about the ethical implications of optogenetics, as well as his belief in the biological basis of all thought and emotion, and how that guides the search for targeted treatments.
Finally, he’ll discuss what he believes NIMH’s top priorities should be, and whether he will blog as did his predecessor, Thomas R. Insel, MD.
On Twitter @whitneymcknight
NEW YORK – In this first of four interviews, the new director of the National Institute of Mental Health, Joshua A. Gordon, MD, PhD, shares his thoughts about the emerging nosology of depression and whether it might be possible to identify and turn off genetic pathways implicated in depression without impacting creativity, sexual drive, and appetite.
Dr. Gordon is a practicing psychiatrist and a neuroscientist whose primary area of research is in the emerging field of optogenetics, which uses light to trace the genetically predetermined neurocircuitry of various mental states through the brain.
He steps into his leadership role with NIMH at a time when some have voiced concern that the institute has placed too much emphasis on future therapies, instead of on what can be done in the here and now to treat mental disorders.
Also in this series, Dr. Gordon discusses how, under his leadership, NIMH will balance the priorities of clinicians in everyday practice with those of researchers. He also explains the finer points of optogenetics. Currently, the technique is being studied only in mouse models; but if it makes it to human trials, researchers will explore the ability to switch on and off certain mental states.
Dr. Gordon talks about the ethical implications of optogenetics, as well as his belief in the biological basis of all thought and emotion, and how that guides the search for targeted treatments.
Finally, he’ll discuss what he believes NIMH’s top priorities should be, and whether he will blog as did his predecessor, Thomas R. Insel, MD.
On Twitter @whitneymcknight
‘Toe and flow’ approach to CLI management lowers amputation risk
Amputation in diabetes is less likely when critical limb ischemia is approached in a multidisciplinary way, according to the coauthor of clinical recommendations issued earlier this year. But to ensure optimal patient outcomes, just who should be on the interdisciplinary care team, how should it be coordinated, and what algorithms are best?
To help navigate these concerns, Joseph L. Mills, MD, professor and chief of vascular surgery and endovascular therapy at Baylor College of Medicine in Houston, will discuss “the toe and flow” model of care on Sunday morning, Sept. 18, as part of the presymposium Addressing Core Questions in Critical Limb Ischemia session.
“This model of care combines podiatrists and orthopedists with vascular specialists who provide advanced open surgery and endovascular therapy, to provide best treatment for patients,” said Dr. Mills, who coauthored the Society for Vascular Surgery Threatened Limb Classification (Wound, Ischemia, and foot Infection), or “WIfI,” as well as a clinical guideline on management of the diabetic foot, released earlier this year by the SVS in collaboration with the American Podiatric Medical Association, and the Society for Vascular Medicine.
Every 20 seconds, somewhere in the world a person with diabetes undergoes leg amputation as a result of the disease, according to Dr. Mills. Not only are the resulting costs of care unmanageable, fragmented diabetic foot care compromises a patient’s quality and longevity of life, he said.
The unfortunate path to amputation in diabetes most commonly begins with a simple neuropathic foot ulcer, often made worse by peripheral artery disease. The wound eventually moves through acute and chronic stages of neuropathy, vasculopathy, and infection, until amputation is necessary. Offering appropriate intervention at any point in this trajectory, or avoiding it altogether, means the ideal care team should include specialists with expertise in these disciplines. Beyond the core team members of a vascular surgeon, podiatrist, and orthopedic specialist, Dr. Mills said that other interdisciplinary team configurations might include a diabetologist, orthopedist, plastic surgeon, infectious disease specialist, general surgeon, and pedorthist/prosthetist.
“Learning how to build ‘toe and flow’ teams into your local environment can help improve outcomes in this challenging patient population,” Dr. Mills said. “Methods and flow diagrams concerning how this can be done will be a major focus of the talk.”
Dr. Mills will cover how patient responsibilities should be divided between team members across varying levels of clinical care, ranging from basic clinics to centers of excellence. The talk will also address aftercare, as well as how to facilitate effective communication between team members and patients.
“Enthusiasm for this model is the key ingredient to helping reduce the number of amputations in your patients,” he said.
On Twitter @whitneymcknight
Amputation in diabetes is less likely when critical limb ischemia is approached in a multidisciplinary way, according to the coauthor of clinical recommendations issued earlier this year. But to ensure optimal patient outcomes, just who should be on the interdisciplinary care team, how should it be coordinated, and what algorithms are best?
To help navigate these concerns, Joseph L. Mills, MD, professor and chief of vascular surgery and endovascular therapy at Baylor College of Medicine in Houston, will discuss “the toe and flow” model of care on Sunday morning, Sept. 18, as part of the presymposium Addressing Core Questions in Critical Limb Ischemia session.
“This model of care combines podiatrists and orthopedists with vascular specialists who provide advanced open surgery and endovascular therapy, to provide best treatment for patients,” said Dr. Mills, who coauthored the Society for Vascular Surgery Threatened Limb Classification (Wound, Ischemia, and foot Infection), or “WIfI,” as well as a clinical guideline on management of the diabetic foot, released earlier this year by the SVS in collaboration with the American Podiatric Medical Association, and the Society for Vascular Medicine.
Every 20 seconds, somewhere in the world a person with diabetes undergoes leg amputation as a result of the disease, according to Dr. Mills. Not only are the resulting costs of care unmanageable, fragmented diabetic foot care compromises a patient’s quality and longevity of life, he said.
The unfortunate path to amputation in diabetes most commonly begins with a simple neuropathic foot ulcer, often made worse by peripheral artery disease. The wound eventually moves through acute and chronic stages of neuropathy, vasculopathy, and infection, until amputation is necessary. Offering appropriate intervention at any point in this trajectory, or avoiding it altogether, means the ideal care team should include specialists with expertise in these disciplines. Beyond the core team members of a vascular surgeon, podiatrist, and orthopedic specialist, Dr. Mills said that other interdisciplinary team configurations might include a diabetologist, orthopedist, plastic surgeon, infectious disease specialist, general surgeon, and pedorthist/prosthetist.
“Learning how to build ‘toe and flow’ teams into your local environment can help improve outcomes in this challenging patient population,” Dr. Mills said. “Methods and flow diagrams concerning how this can be done will be a major focus of the talk.”
Dr. Mills will cover how patient responsibilities should be divided between team members across varying levels of clinical care, ranging from basic clinics to centers of excellence. The talk will also address aftercare, as well as how to facilitate effective communication between team members and patients.
“Enthusiasm for this model is the key ingredient to helping reduce the number of amputations in your patients,” he said.
On Twitter @whitneymcknight
Amputation in diabetes is less likely when critical limb ischemia is approached in a multidisciplinary way, according to the coauthor of clinical recommendations issued earlier this year. But to ensure optimal patient outcomes, just who should be on the interdisciplinary care team, how should it be coordinated, and what algorithms are best?
To help navigate these concerns, Joseph L. Mills, MD, professor and chief of vascular surgery and endovascular therapy at Baylor College of Medicine in Houston, will discuss “the toe and flow” model of care on Sunday morning, Sept. 18, as part of the presymposium Addressing Core Questions in Critical Limb Ischemia session.
“This model of care combines podiatrists and orthopedists with vascular specialists who provide advanced open surgery and endovascular therapy, to provide best treatment for patients,” said Dr. Mills, who coauthored the Society for Vascular Surgery Threatened Limb Classification (Wound, Ischemia, and foot Infection), or “WIfI,” as well as a clinical guideline on management of the diabetic foot, released earlier this year by the SVS in collaboration with the American Podiatric Medical Association, and the Society for Vascular Medicine.
Every 20 seconds, somewhere in the world a person with diabetes undergoes leg amputation as a result of the disease, according to Dr. Mills. Not only are the resulting costs of care unmanageable, fragmented diabetic foot care compromises a patient’s quality and longevity of life, he said.
The unfortunate path to amputation in diabetes most commonly begins with a simple neuropathic foot ulcer, often made worse by peripheral artery disease. The wound eventually moves through acute and chronic stages of neuropathy, vasculopathy, and infection, until amputation is necessary. Offering appropriate intervention at any point in this trajectory, or avoiding it altogether, means the ideal care team should include specialists with expertise in these disciplines. Beyond the core team members of a vascular surgeon, podiatrist, and orthopedic specialist, Dr. Mills said that other interdisciplinary team configurations might include a diabetologist, orthopedist, plastic surgeon, infectious disease specialist, general surgeon, and pedorthist/prosthetist.
“Learning how to build ‘toe and flow’ teams into your local environment can help improve outcomes in this challenging patient population,” Dr. Mills said. “Methods and flow diagrams concerning how this can be done will be a major focus of the talk.”
Dr. Mills will cover how patient responsibilities should be divided between team members across varying levels of clinical care, ranging from basic clinics to centers of excellence. The talk will also address aftercare, as well as how to facilitate effective communication between team members and patients.
“Enthusiasm for this model is the key ingredient to helping reduce the number of amputations in your patients,” he said.
On Twitter @whitneymcknight
New drugs poised to stem tide of antibacterial resistance in gonorrhea
ANNAPOLIS, MD. – Three novel treatments for gonorrhea, currently in late stages of development, could give clinicians an edge in the fight against antibacterial resistance, according to a federal health official.
The pathogen Neisseria gonorrhoeae is already showing signs of besting first-line therapy ceftriaxone in Japan and parts of Europe, said Carolyn Deal, PhD, chief of the sexually transmitted diseases branch at the National Institute of Allergy and Infectious Diseases (NIAID). And the Centers for Disease Control and Prevention lists N. gonorrhoeae among its “urgent” antibiotic resistance threats.
“I think we have a new superbug,” Dr. Deal said at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology. “In my opinion, it’s just a matter of time in this country.”
But three agents in late-stage clinical trials for uncomplicated urogenital gonorrhea offer promise in fighting the gram-negative bacteria, according to Dr. Deal. The first is solithromycin, manufactured by Cempra. The company has a phase III study underway to compare a single dose of oral solithromycin with intramuscular ceftriaxone plus oral azithromycin for urogenital gonorrhea.
The other two drugs are first-in-class antibacterial agents. In partnership with the NIAID, the company Entasis recently completed a phase II study of zoliflodacin, an oral agent in a novel class of topoisomerase inhibitors. A phase III trial is expected to begin in 2017, also in partnership with the NIAID, according to an Entasis document. The third agent is gepotidacin, a novel triazaacenaphthylene antibacterial agent currently being investigated by GlaxoSmithKline in a phase II study.
Because N. gonorrhoeae poses such an urgent threat, waiting to develop a vaccine is less feasible than working with companies to develop additional antibacterial agents, Dr. Deal said. But taking a compound out of the basic research lab and having enough data to get into the investigational new drug phase is a significant investment, she said, so pharmaceutical manufacturers look for as many indications for a drug as possible.
For instance, solithromycin was initially investigated for community-acquired pneumonia. Gepotidacin initially was developed in partnership with the NIAID and the Biomedical Advanced Research and Development Authority in case of an anthrax attack, Dr. Deal said. “The Entasis product is the only one specifically developed for Neisseria gonorrhoeae,” she said.
One reason that two of the drugs in the pipeline include N. gonorrhoeae as an indication is that the Food and Drug Administration has issued guidance on developing drugs in the area of uncomplicated gonorrhea. That guidance is lacking for nasopharyngeal and rectal gonorrhea, leaving a “vacuum” in the pipeline, Dr. Deal said. “Many of us have come to the conclusion that developing vaccines is the only real long-term solution.”
On Twitter @whitneymcknight
ANNAPOLIS, MD. – Three novel treatments for gonorrhea, currently in late stages of development, could give clinicians an edge in the fight against antibacterial resistance, according to a federal health official.
The pathogen Neisseria gonorrhoeae is already showing signs of besting first-line therapy ceftriaxone in Japan and parts of Europe, said Carolyn Deal, PhD, chief of the sexually transmitted diseases branch at the National Institute of Allergy and Infectious Diseases (NIAID). And the Centers for Disease Control and Prevention lists N. gonorrhoeae among its “urgent” antibiotic resistance threats.
“I think we have a new superbug,” Dr. Deal said at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology. “In my opinion, it’s just a matter of time in this country.”
But three agents in late-stage clinical trials for uncomplicated urogenital gonorrhea offer promise in fighting the gram-negative bacteria, according to Dr. Deal. The first is solithromycin, manufactured by Cempra. The company has a phase III study underway to compare a single dose of oral solithromycin with intramuscular ceftriaxone plus oral azithromycin for urogenital gonorrhea.
The other two drugs are first-in-class antibacterial agents. In partnership with the NIAID, the company Entasis recently completed a phase II study of zoliflodacin, an oral agent in a novel class of topoisomerase inhibitors. A phase III trial is expected to begin in 2017, also in partnership with the NIAID, according to an Entasis document. The third agent is gepotidacin, a novel triazaacenaphthylene antibacterial agent currently being investigated by GlaxoSmithKline in a phase II study.
Because N. gonorrhoeae poses such an urgent threat, waiting to develop a vaccine is less feasible than working with companies to develop additional antibacterial agents, Dr. Deal said. But taking a compound out of the basic research lab and having enough data to get into the investigational new drug phase is a significant investment, she said, so pharmaceutical manufacturers look for as many indications for a drug as possible.
For instance, solithromycin was initially investigated for community-acquired pneumonia. Gepotidacin initially was developed in partnership with the NIAID and the Biomedical Advanced Research and Development Authority in case of an anthrax attack, Dr. Deal said. “The Entasis product is the only one specifically developed for Neisseria gonorrhoeae,” she said.
One reason that two of the drugs in the pipeline include N. gonorrhoeae as an indication is that the Food and Drug Administration has issued guidance on developing drugs in the area of uncomplicated gonorrhea. That guidance is lacking for nasopharyngeal and rectal gonorrhea, leaving a “vacuum” in the pipeline, Dr. Deal said. “Many of us have come to the conclusion that developing vaccines is the only real long-term solution.”
On Twitter @whitneymcknight
ANNAPOLIS, MD. – Three novel treatments for gonorrhea, currently in late stages of development, could give clinicians an edge in the fight against antibacterial resistance, according to a federal health official.
The pathogen Neisseria gonorrhoeae is already showing signs of besting first-line therapy ceftriaxone in Japan and parts of Europe, said Carolyn Deal, PhD, chief of the sexually transmitted diseases branch at the National Institute of Allergy and Infectious Diseases (NIAID). And the Centers for Disease Control and Prevention lists N. gonorrhoeae among its “urgent” antibiotic resistance threats.
“I think we have a new superbug,” Dr. Deal said at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology. “In my opinion, it’s just a matter of time in this country.”
But three agents in late-stage clinical trials for uncomplicated urogenital gonorrhea offer promise in fighting the gram-negative bacteria, according to Dr. Deal. The first is solithromycin, manufactured by Cempra. The company has a phase III study underway to compare a single dose of oral solithromycin with intramuscular ceftriaxone plus oral azithromycin for urogenital gonorrhea.
The other two drugs are first-in-class antibacterial agents. In partnership with the NIAID, the company Entasis recently completed a phase II study of zoliflodacin, an oral agent in a novel class of topoisomerase inhibitors. A phase III trial is expected to begin in 2017, also in partnership with the NIAID, according to an Entasis document. The third agent is gepotidacin, a novel triazaacenaphthylene antibacterial agent currently being investigated by GlaxoSmithKline in a phase II study.
Because N. gonorrhoeae poses such an urgent threat, waiting to develop a vaccine is less feasible than working with companies to develop additional antibacterial agents, Dr. Deal said. But taking a compound out of the basic research lab and having enough data to get into the investigational new drug phase is a significant investment, she said, so pharmaceutical manufacturers look for as many indications for a drug as possible.
For instance, solithromycin was initially investigated for community-acquired pneumonia. Gepotidacin initially was developed in partnership with the NIAID and the Biomedical Advanced Research and Development Authority in case of an anthrax attack, Dr. Deal said. “The Entasis product is the only one specifically developed for Neisseria gonorrhoeae,” she said.
One reason that two of the drugs in the pipeline include N. gonorrhoeae as an indication is that the Food and Drug Administration has issued guidance on developing drugs in the area of uncomplicated gonorrhea. That guidance is lacking for nasopharyngeal and rectal gonorrhea, leaving a “vacuum” in the pipeline, Dr. Deal said. “Many of us have come to the conclusion that developing vaccines is the only real long-term solution.”
On Twitter @whitneymcknight
EXPERT ANALYSIS FROM IDSOG
VIDEO: When geriatric depression turns psychotic
A geriatric patient who recently lost his wife presents with significant weight loss and appears disheveled. He speaks of reuniting with his wife as soon as possible. How do you quickly stabilize this patient who appears to be experiencing psychotic depression?
In this installment of Mental Health Consult, our panel members discuss their recommendations for triaging a 65-year-old recently widowed man with a history of prostate cancer but no prior history of psychosis.
Join our panel of experts from George Washington University, Washington, including Katalin Roth, MD, director of geriatrics and palliative medicine; April Barbour, MD, MPH, director of the division of general internal medicine; and Lorenzo Norris, MD, medical director of psychiatric and behavioral services, as they discuss how to effectively deal with a geriatric patient in crisis.
On Twitter @whitneymcknight
A geriatric patient who recently lost his wife presents with significant weight loss and appears disheveled. He speaks of reuniting with his wife as soon as possible. How do you quickly stabilize this patient who appears to be experiencing psychotic depression?
In this installment of Mental Health Consult, our panel members discuss their recommendations for triaging a 65-year-old recently widowed man with a history of prostate cancer but no prior history of psychosis.
Join our panel of experts from George Washington University, Washington, including Katalin Roth, MD, director of geriatrics and palliative medicine; April Barbour, MD, MPH, director of the division of general internal medicine; and Lorenzo Norris, MD, medical director of psychiatric and behavioral services, as they discuss how to effectively deal with a geriatric patient in crisis.
On Twitter @whitneymcknight
A geriatric patient who recently lost his wife presents with significant weight loss and appears disheveled. He speaks of reuniting with his wife as soon as possible. How do you quickly stabilize this patient who appears to be experiencing psychotic depression?
In this installment of Mental Health Consult, our panel members discuss their recommendations for triaging a 65-year-old recently widowed man with a history of prostate cancer but no prior history of psychosis.
Join our panel of experts from George Washington University, Washington, including Katalin Roth, MD, director of geriatrics and palliative medicine; April Barbour, MD, MPH, director of the division of general internal medicine; and Lorenzo Norris, MD, medical director of psychiatric and behavioral services, as they discuss how to effectively deal with a geriatric patient in crisis.
On Twitter @whitneymcknight
Type 2 diabetes peer-led intervention in primary care tied to improved depression symptoms
BETHESDA, MD. – A novel, peer- and nurse-led intervention in a primary care setting for type 2 diabetes in people with serious mental illness was associated with improvements in depression symptoms, global psychopathology, and overall health, a study has shown.
“The intervention really is patient self-management. It could be a nice complement to team-based, multidisciplinary care,” said Martha Sajatovic, MD, who presented the data in a poster at a National Institute of Mental Health conference on mental health services research. Dr. Sajatovic is the Willard W. Brown Chair and director of the Neurological & Behavioral Outcomes Center at University Hospitals Neurological Institute in Cleveland.
People with serious mental illness (SMI) have a significantly higher risk of premature death than do those in the general population, in part because this cohort experiences higher rates of metabolic disease, often exacerbated by higher rates of smoking, poor diet, substance abuse, and lack of exercise. However, in a 60-week randomized controlled trial of 200 people with SMI and comorbid type 2 diabetes, which was conducted in a primary care setting, those who were taught better self-care fared better than did those who received treatment as usual.
The group-based, psychosocial intervention – called “targeted training in illness” – blended psychoeducation, problem identification, goal setting, behavioral modeling, and care coordination around SMI and diabetes. In the first 12 weeks, groups of 6-10 people met in weekly, hour-long sessions co-led by a peer and nurse educator. Group discussions focused on self-management of diabetes through proper eating habits, regular exercise, tobacco cessation, and other forms of behavior modification.
Meeting as a group helped to “combat some of the social isolation that you see in this population,” Dr. Sajatovic said in an interview. “The peer leadership is really critical, too, because it empowers [the participants]. I believe peer support gives resilience ... and helps [the group] see you don’t have to be perfect to make progress.” In the study, the 3 months of group sessions were followed by weekly telephone maintenance sessions with either the peer or nurse educator for 48 weeks.
Half of the study’s participants – two-thirds of whom were women, and just over half of whom were black – had had a diagnosis of diabetes for at least 10 years; half of all participants used insulin. All had either schizophrenia, schizoaffective disorder, bipolar disorder, or major depressive disorder. Baseline rates of depression were high, and psychotic symptoms were minimal.
After assessments at baseline, 13, 30, and 60 weeks, the study arm was found to have improvements in depression, global psychopathology, and functional status, which Dr. Sajatovic said could be attributable to the group’s significantly improved knowledge about diabetes (P less than .01).
Glycemic control improved generally, a surprising finding that Dr. Sajatovic said could have been tied to the expansion of Medicaid in Ohio, where the study was done, and a “real concerted effort” to provide treatment by medical homes at this time.
While no significant difference between the groups was found overall, a post hoc analysis showed a difference in the 53% of the entire sample who had good to fair glycemic control (hemoglobin A1c equal to or less than 7.5) at baseline: At 60 weeks, those in the treatment arm achieved stable, long-term control compared with controls, whose values had worsened slightly (P = .024). Those people tended to be older, more likely to have schizophrenia, and less likely to be on insulin, and to have a shorter history of diabetes, said Dr. Sajatovic, professor of psychiatry and of neurology at Case Western Reserve University, Cleveland.
Compared with controls, the study arm had greater improvement at 60 weeks in Clinical Global Impression scores (P = .0008); Montgomery-Åsberg Depression Rating Scale scores (P = .0156); Global Assessment of Functioning scores (P = .0031); and knowledge of diabetes (P less than .0002), as well as an improvement trend in Sheehan Disability Scale scores (P = .0863). There was no difference between the groups on the Brief Psychiatric Rating Scale, the Short Form–36 or HbA1c values. By study’s end, Dr. Sajatovic said about a quarter had been lost to follow-up.
The intervention meets three important criteria, she said. “First, people need to know what to do. Then, they need to have confidence, or self-efficacy. The third thing is that the person has to believe in a given outcome based on a given behavior.”
Dr. Sajatovic did not have any relevant disclosures. The National Institutes of Health funded the study.
On Twitter @whitneymcknight
BETHESDA, MD. – A novel, peer- and nurse-led intervention in a primary care setting for type 2 diabetes in people with serious mental illness was associated with improvements in depression symptoms, global psychopathology, and overall health, a study has shown.
“The intervention really is patient self-management. It could be a nice complement to team-based, multidisciplinary care,” said Martha Sajatovic, MD, who presented the data in a poster at a National Institute of Mental Health conference on mental health services research. Dr. Sajatovic is the Willard W. Brown Chair and director of the Neurological & Behavioral Outcomes Center at University Hospitals Neurological Institute in Cleveland.
People with serious mental illness (SMI) have a significantly higher risk of premature death than do those in the general population, in part because this cohort experiences higher rates of metabolic disease, often exacerbated by higher rates of smoking, poor diet, substance abuse, and lack of exercise. However, in a 60-week randomized controlled trial of 200 people with SMI and comorbid type 2 diabetes, which was conducted in a primary care setting, those who were taught better self-care fared better than did those who received treatment as usual.
The group-based, psychosocial intervention – called “targeted training in illness” – blended psychoeducation, problem identification, goal setting, behavioral modeling, and care coordination around SMI and diabetes. In the first 12 weeks, groups of 6-10 people met in weekly, hour-long sessions co-led by a peer and nurse educator. Group discussions focused on self-management of diabetes through proper eating habits, regular exercise, tobacco cessation, and other forms of behavior modification.
Meeting as a group helped to “combat some of the social isolation that you see in this population,” Dr. Sajatovic said in an interview. “The peer leadership is really critical, too, because it empowers [the participants]. I believe peer support gives resilience ... and helps [the group] see you don’t have to be perfect to make progress.” In the study, the 3 months of group sessions were followed by weekly telephone maintenance sessions with either the peer or nurse educator for 48 weeks.
Half of the study’s participants – two-thirds of whom were women, and just over half of whom were black – had had a diagnosis of diabetes for at least 10 years; half of all participants used insulin. All had either schizophrenia, schizoaffective disorder, bipolar disorder, or major depressive disorder. Baseline rates of depression were high, and psychotic symptoms were minimal.
After assessments at baseline, 13, 30, and 60 weeks, the study arm was found to have improvements in depression, global psychopathology, and functional status, which Dr. Sajatovic said could be attributable to the group’s significantly improved knowledge about diabetes (P less than .01).
Glycemic control improved generally, a surprising finding that Dr. Sajatovic said could have been tied to the expansion of Medicaid in Ohio, where the study was done, and a “real concerted effort” to provide treatment by medical homes at this time.
While no significant difference between the groups was found overall, a post hoc analysis showed a difference in the 53% of the entire sample who had good to fair glycemic control (hemoglobin A1c equal to or less than 7.5) at baseline: At 60 weeks, those in the treatment arm achieved stable, long-term control compared with controls, whose values had worsened slightly (P = .024). Those people tended to be older, more likely to have schizophrenia, and less likely to be on insulin, and to have a shorter history of diabetes, said Dr. Sajatovic, professor of psychiatry and of neurology at Case Western Reserve University, Cleveland.
Compared with controls, the study arm had greater improvement at 60 weeks in Clinical Global Impression scores (P = .0008); Montgomery-Åsberg Depression Rating Scale scores (P = .0156); Global Assessment of Functioning scores (P = .0031); and knowledge of diabetes (P less than .0002), as well as an improvement trend in Sheehan Disability Scale scores (P = .0863). There was no difference between the groups on the Brief Psychiatric Rating Scale, the Short Form–36 or HbA1c values. By study’s end, Dr. Sajatovic said about a quarter had been lost to follow-up.
The intervention meets three important criteria, she said. “First, people need to know what to do. Then, they need to have confidence, or self-efficacy. The third thing is that the person has to believe in a given outcome based on a given behavior.”
Dr. Sajatovic did not have any relevant disclosures. The National Institutes of Health funded the study.
On Twitter @whitneymcknight
BETHESDA, MD. – A novel, peer- and nurse-led intervention in a primary care setting for type 2 diabetes in people with serious mental illness was associated with improvements in depression symptoms, global psychopathology, and overall health, a study has shown.
“The intervention really is patient self-management. It could be a nice complement to team-based, multidisciplinary care,” said Martha Sajatovic, MD, who presented the data in a poster at a National Institute of Mental Health conference on mental health services research. Dr. Sajatovic is the Willard W. Brown Chair and director of the Neurological & Behavioral Outcomes Center at University Hospitals Neurological Institute in Cleveland.
People with serious mental illness (SMI) have a significantly higher risk of premature death than do those in the general population, in part because this cohort experiences higher rates of metabolic disease, often exacerbated by higher rates of smoking, poor diet, substance abuse, and lack of exercise. However, in a 60-week randomized controlled trial of 200 people with SMI and comorbid type 2 diabetes, which was conducted in a primary care setting, those who were taught better self-care fared better than did those who received treatment as usual.
The group-based, psychosocial intervention – called “targeted training in illness” – blended psychoeducation, problem identification, goal setting, behavioral modeling, and care coordination around SMI and diabetes. In the first 12 weeks, groups of 6-10 people met in weekly, hour-long sessions co-led by a peer and nurse educator. Group discussions focused on self-management of diabetes through proper eating habits, regular exercise, tobacco cessation, and other forms of behavior modification.
Meeting as a group helped to “combat some of the social isolation that you see in this population,” Dr. Sajatovic said in an interview. “The peer leadership is really critical, too, because it empowers [the participants]. I believe peer support gives resilience ... and helps [the group] see you don’t have to be perfect to make progress.” In the study, the 3 months of group sessions were followed by weekly telephone maintenance sessions with either the peer or nurse educator for 48 weeks.
Half of the study’s participants – two-thirds of whom were women, and just over half of whom were black – had had a diagnosis of diabetes for at least 10 years; half of all participants used insulin. All had either schizophrenia, schizoaffective disorder, bipolar disorder, or major depressive disorder. Baseline rates of depression were high, and psychotic symptoms were minimal.
After assessments at baseline, 13, 30, and 60 weeks, the study arm was found to have improvements in depression, global psychopathology, and functional status, which Dr. Sajatovic said could be attributable to the group’s significantly improved knowledge about diabetes (P less than .01).
Glycemic control improved generally, a surprising finding that Dr. Sajatovic said could have been tied to the expansion of Medicaid in Ohio, where the study was done, and a “real concerted effort” to provide treatment by medical homes at this time.
While no significant difference between the groups was found overall, a post hoc analysis showed a difference in the 53% of the entire sample who had good to fair glycemic control (hemoglobin A1c equal to or less than 7.5) at baseline: At 60 weeks, those in the treatment arm achieved stable, long-term control compared with controls, whose values had worsened slightly (P = .024). Those people tended to be older, more likely to have schizophrenia, and less likely to be on insulin, and to have a shorter history of diabetes, said Dr. Sajatovic, professor of psychiatry and of neurology at Case Western Reserve University, Cleveland.
Compared with controls, the study arm had greater improvement at 60 weeks in Clinical Global Impression scores (P = .0008); Montgomery-Åsberg Depression Rating Scale scores (P = .0156); Global Assessment of Functioning scores (P = .0031); and knowledge of diabetes (P less than .0002), as well as an improvement trend in Sheehan Disability Scale scores (P = .0863). There was no difference between the groups on the Brief Psychiatric Rating Scale, the Short Form–36 or HbA1c values. By study’s end, Dr. Sajatovic said about a quarter had been lost to follow-up.
The intervention meets three important criteria, she said. “First, people need to know what to do. Then, they need to have confidence, or self-efficacy. The third thing is that the person has to believe in a given outcome based on a given behavior.”
Dr. Sajatovic did not have any relevant disclosures. The National Institutes of Health funded the study.
On Twitter @whitneymcknight
AT AN NIMH CONFERENCE
Key clinical point: Targeted training in illness management effectively improves overall health outcomes in people with serious mental illness and comorbid type 2 diabetes.
Major finding: Compared with treatment as usual, peer-led intervention improved depression, overall health, and knowledge of diabetes at 60 weeks.
Data source: Randomized, controlled study of 200 people with serious mental illness and comorbid type 2 diabetes seen in primary care.
Disclosures: Dr. Sajatovic did not have any relevant disclosures. The National Institutes of Health funded the study.
Single dose bacterial vaginosis treatment performs well in phase III trial
ANNAPOLIS, MD. – Women with bacterial vaginosis could soon have an effective oral, single-dose treatment option, if results of a phase III study result in approval by the Food and Drug Administration.
In a modified intention-to-treat study of 189 women with bacterial vaginosis (BV) randomly assigned 2:1 to treatment or placebo, a single, granulated oral dose of secnidazole 2g was found to be statistically superior to placebo on all clinical endpoints.
Secnidazole (SYM-1219) has a longer half-life, compared with metronidazole, the current treatment standard, according to Jane R. Schwebke, MD, the study investigator and a professor of medicine in the infectious disease department of the University of Alabama, Birmingham. Dr. Schwebke credits the study drug’s high bioavailablility and rapid absorption for its efficacy.
“You get a very high peak with SYM-1219 initially, and I think that might be the reason for the single-dose therapy’s efficacy. It’s due to the pharmacokinetics of the drug itself,” she reported at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology.
If the drug is approved, it would likely mean better adherence when compared with current standards of treatment, according to Sharon Hillier, PhD, director of reproductive infectious disease research at the Magee-Women’s Hospital of the University of Pittsburgh.
“It will absolutely improve compliance,” Dr. Hillier said in an interview. “Obviously, it’s much easier than taking [metronidazole] twice a day for 7 days.”
Treatment with metronidazole also requires a week of abstinence from alcohol, compared with what Dr. Hillier anticipates would be 2 or 3 days of alcohol abstinence with secnidazole.
The initial study enrollment was 189 women who were randomized 2:1 to secnidazole or placebo and treated at 21 sites nationally. After assessment for common sexually transmitted diseases, Nugent scores of 4 or greater, and all Amsel criteria (including a vaginal pH of 4.7 or greater, clue cells at or greater than 20%, and a positive KOH whiff test), 164 women remained in the modified intention-to-treat (ITT) analysis. A quarter of all women across the modified ITT group were recurrent BV sufferers, having had at least four episodes of BV in the previous year, and 87% had Nugent scores of 7 or greater.
“These were true BV cases; none were in the intermediate or mild zone,” Dr. Schwebke said.
Responders were women who, between days 21 and 30, had “normal” discharge, less than 20% clue cells, and a negative KOH whiff test. In the study arm, 53.3% of women had “normal” discharge and less than 20% clue cells at their 21-30 day visit, compared with 19.3% in the placebo group (P less than .001). The secondary endpoint – Nugent scores of 3 or less at days 7-14 – was achieved by 43.9% in the study group, compared with 5.3% of controls (P less than .001).
Just over a third of women in the study arm experienced one or more adverse events, compared with 21.9% of controls. Yeast infections were the most common adverse event. Less than 5% of the study group experienced nausea, headache, or diarrhea, compared with up to 3% of controls.
“What’s exciting about this new product is that it will be a single dose oral [that women] can take with a meal and with none of the adverse effects, and it relieves symptoms as well as other treatments,” Dr. Hillier said.
How treatment efficacy should be defined was a matter of debate during the presentation’s question and answer period. The FDA did not issue BV treatment guidance until 1998, despite prior approval of BV treatments clindamycin and metronidazole. The rigorous definition of clinical cure rate put forward in the FDA guidance document caused the cure rates that had been generally accepted by physicians to drop from as high as 80% to around 40%, according to Dr. Hilliard.
“I personally would like to see some head-to-head comparisons of the various treatments we have to know whether some are better than others,” Dr. Hillier said in the interview.
The ideal BV treatment should also provoke a microbiological cure, according to Dr. Schwebke. “What I would do is combine a drug like this with a biofilm inhibitor. Right now, this is great, because it’s single dose oral, and it’s as good as anything out there, but, I don’t think we’re taking the next step necessarily with efficacy.”
The study was supported by Symbiomix. Dr. Schwebke is a consultant for Symbiomix and receives funding from Alfa Wassermann and Starpharma, among others. Dr. Hillier is coprincipal investigator of the Microbicide Trials Network, sponsored by the National Institutes of Health.
On Twitter @whitneymcknight
ANNAPOLIS, MD. – Women with bacterial vaginosis could soon have an effective oral, single-dose treatment option, if results of a phase III study result in approval by the Food and Drug Administration.
In a modified intention-to-treat study of 189 women with bacterial vaginosis (BV) randomly assigned 2:1 to treatment or placebo, a single, granulated oral dose of secnidazole 2g was found to be statistically superior to placebo on all clinical endpoints.
Secnidazole (SYM-1219) has a longer half-life, compared with metronidazole, the current treatment standard, according to Jane R. Schwebke, MD, the study investigator and a professor of medicine in the infectious disease department of the University of Alabama, Birmingham. Dr. Schwebke credits the study drug’s high bioavailablility and rapid absorption for its efficacy.
“You get a very high peak with SYM-1219 initially, and I think that might be the reason for the single-dose therapy’s efficacy. It’s due to the pharmacokinetics of the drug itself,” she reported at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology.
If the drug is approved, it would likely mean better adherence when compared with current standards of treatment, according to Sharon Hillier, PhD, director of reproductive infectious disease research at the Magee-Women’s Hospital of the University of Pittsburgh.
“It will absolutely improve compliance,” Dr. Hillier said in an interview. “Obviously, it’s much easier than taking [metronidazole] twice a day for 7 days.”
Treatment with metronidazole also requires a week of abstinence from alcohol, compared with what Dr. Hillier anticipates would be 2 or 3 days of alcohol abstinence with secnidazole.
The initial study enrollment was 189 women who were randomized 2:1 to secnidazole or placebo and treated at 21 sites nationally. After assessment for common sexually transmitted diseases, Nugent scores of 4 or greater, and all Amsel criteria (including a vaginal pH of 4.7 or greater, clue cells at or greater than 20%, and a positive KOH whiff test), 164 women remained in the modified intention-to-treat (ITT) analysis. A quarter of all women across the modified ITT group were recurrent BV sufferers, having had at least four episodes of BV in the previous year, and 87% had Nugent scores of 7 or greater.
“These were true BV cases; none were in the intermediate or mild zone,” Dr. Schwebke said.
Responders were women who, between days 21 and 30, had “normal” discharge, less than 20% clue cells, and a negative KOH whiff test. In the study arm, 53.3% of women had “normal” discharge and less than 20% clue cells at their 21-30 day visit, compared with 19.3% in the placebo group (P less than .001). The secondary endpoint – Nugent scores of 3 or less at days 7-14 – was achieved by 43.9% in the study group, compared with 5.3% of controls (P less than .001).
Just over a third of women in the study arm experienced one or more adverse events, compared with 21.9% of controls. Yeast infections were the most common adverse event. Less than 5% of the study group experienced nausea, headache, or diarrhea, compared with up to 3% of controls.
“What’s exciting about this new product is that it will be a single dose oral [that women] can take with a meal and with none of the adverse effects, and it relieves symptoms as well as other treatments,” Dr. Hillier said.
How treatment efficacy should be defined was a matter of debate during the presentation’s question and answer period. The FDA did not issue BV treatment guidance until 1998, despite prior approval of BV treatments clindamycin and metronidazole. The rigorous definition of clinical cure rate put forward in the FDA guidance document caused the cure rates that had been generally accepted by physicians to drop from as high as 80% to around 40%, according to Dr. Hilliard.
“I personally would like to see some head-to-head comparisons of the various treatments we have to know whether some are better than others,” Dr. Hillier said in the interview.
The ideal BV treatment should also provoke a microbiological cure, according to Dr. Schwebke. “What I would do is combine a drug like this with a biofilm inhibitor. Right now, this is great, because it’s single dose oral, and it’s as good as anything out there, but, I don’t think we’re taking the next step necessarily with efficacy.”
The study was supported by Symbiomix. Dr. Schwebke is a consultant for Symbiomix and receives funding from Alfa Wassermann and Starpharma, among others. Dr. Hillier is coprincipal investigator of the Microbicide Trials Network, sponsored by the National Institutes of Health.
On Twitter @whitneymcknight
ANNAPOLIS, MD. – Women with bacterial vaginosis could soon have an effective oral, single-dose treatment option, if results of a phase III study result in approval by the Food and Drug Administration.
In a modified intention-to-treat study of 189 women with bacterial vaginosis (BV) randomly assigned 2:1 to treatment or placebo, a single, granulated oral dose of secnidazole 2g was found to be statistically superior to placebo on all clinical endpoints.
Secnidazole (SYM-1219) has a longer half-life, compared with metronidazole, the current treatment standard, according to Jane R. Schwebke, MD, the study investigator and a professor of medicine in the infectious disease department of the University of Alabama, Birmingham. Dr. Schwebke credits the study drug’s high bioavailablility and rapid absorption for its efficacy.
“You get a very high peak with SYM-1219 initially, and I think that might be the reason for the single-dose therapy’s efficacy. It’s due to the pharmacokinetics of the drug itself,” she reported at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology.
If the drug is approved, it would likely mean better adherence when compared with current standards of treatment, according to Sharon Hillier, PhD, director of reproductive infectious disease research at the Magee-Women’s Hospital of the University of Pittsburgh.
“It will absolutely improve compliance,” Dr. Hillier said in an interview. “Obviously, it’s much easier than taking [metronidazole] twice a day for 7 days.”
Treatment with metronidazole also requires a week of abstinence from alcohol, compared with what Dr. Hillier anticipates would be 2 or 3 days of alcohol abstinence with secnidazole.
The initial study enrollment was 189 women who were randomized 2:1 to secnidazole or placebo and treated at 21 sites nationally. After assessment for common sexually transmitted diseases, Nugent scores of 4 or greater, and all Amsel criteria (including a vaginal pH of 4.7 or greater, clue cells at or greater than 20%, and a positive KOH whiff test), 164 women remained in the modified intention-to-treat (ITT) analysis. A quarter of all women across the modified ITT group were recurrent BV sufferers, having had at least four episodes of BV in the previous year, and 87% had Nugent scores of 7 or greater.
“These were true BV cases; none were in the intermediate or mild zone,” Dr. Schwebke said.
Responders were women who, between days 21 and 30, had “normal” discharge, less than 20% clue cells, and a negative KOH whiff test. In the study arm, 53.3% of women had “normal” discharge and less than 20% clue cells at their 21-30 day visit, compared with 19.3% in the placebo group (P less than .001). The secondary endpoint – Nugent scores of 3 or less at days 7-14 – was achieved by 43.9% in the study group, compared with 5.3% of controls (P less than .001).
Just over a third of women in the study arm experienced one or more adverse events, compared with 21.9% of controls. Yeast infections were the most common adverse event. Less than 5% of the study group experienced nausea, headache, or diarrhea, compared with up to 3% of controls.
“What’s exciting about this new product is that it will be a single dose oral [that women] can take with a meal and with none of the adverse effects, and it relieves symptoms as well as other treatments,” Dr. Hillier said.
How treatment efficacy should be defined was a matter of debate during the presentation’s question and answer period. The FDA did not issue BV treatment guidance until 1998, despite prior approval of BV treatments clindamycin and metronidazole. The rigorous definition of clinical cure rate put forward in the FDA guidance document caused the cure rates that had been generally accepted by physicians to drop from as high as 80% to around 40%, according to Dr. Hilliard.
“I personally would like to see some head-to-head comparisons of the various treatments we have to know whether some are better than others,” Dr. Hillier said in the interview.
The ideal BV treatment should also provoke a microbiological cure, according to Dr. Schwebke. “What I would do is combine a drug like this with a biofilm inhibitor. Right now, this is great, because it’s single dose oral, and it’s as good as anything out there, but, I don’t think we’re taking the next step necessarily with efficacy.”
The study was supported by Symbiomix. Dr. Schwebke is a consultant for Symbiomix and receives funding from Alfa Wassermann and Starpharma, among others. Dr. Hillier is coprincipal investigator of the Microbicide Trials Network, sponsored by the National Institutes of Health.
On Twitter @whitneymcknight
AT IDSOG
Key clinical point: Granulated, single-dose oral secnidazole was statistically superior to placebo in treating bacterial vaginosis.
Major finding: In the study arm, 53.3% of women had “normal” discharge and less than 20% clue cells at their 21-30 day visit, compared with 19.3% in the placebo group (P less than .001).
Data source: A randomized, controlled phase III study of 189 women with bacterial vaginosis.
Disclosures: The study was supported by Symbiomix. Dr. Schwebke is a consultant for Symbiomix and receives funding from Alfa Wassermann and Starpharma, among others. Dr. Hillier is coprincipal investigator of the Microbicide Trials Network, sponsored by the National Institutes of Health.
Serious infections in second trimester increase epilepsy risk
ANNAPOLIS, MD. – Febrile infections occurring in the second trimester appear to pose the greatest risk to the neurodevelopment of the fetus, a population based cohort study has shown.
In a review of 8,618,171 California births between January 1991 and December 2008, Ms. Hilary Haber, a third-year medical student at the University of California, Davis, and her coinvestigators found that maternal infections requiring hospitalizations during the second trimester were associated with a relative risk of 2.5 of having a child with epilepsy, a relative risk of 2.3 of having a child with an intellectual disability, and a relative risk of 1.2 of having a child with autism.
Significant associations were observed between subcategories of infection and intellectual disability and epilepsy, particularly those of a bacterial cause and from respiratory and genitourinary sites. Overall, any maternal infection during pregnancy was associated with a 43% increased risk of epilepsy, a 33% increased risk of intellectual disability, and an 8% increased risk of autism.
The exact mechanism of action between the maternal infection and adverse fetal neurodevelopmental outcomes is still unclear, Ms. Haber said at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology.
“Next, we are considering which specific [maternal] infections we should look at,” Ms. Haber said in an interview. “There is something about febrile infections, so we want to narrow that down and better characterize the outcomes from mild, moderate, severe infections.”
Ms. Haber reported having no relevant financial disclosures.
On Twitter @whitneymcknight
ANNAPOLIS, MD. – Febrile infections occurring in the second trimester appear to pose the greatest risk to the neurodevelopment of the fetus, a population based cohort study has shown.
In a review of 8,618,171 California births between January 1991 and December 2008, Ms. Hilary Haber, a third-year medical student at the University of California, Davis, and her coinvestigators found that maternal infections requiring hospitalizations during the second trimester were associated with a relative risk of 2.5 of having a child with epilepsy, a relative risk of 2.3 of having a child with an intellectual disability, and a relative risk of 1.2 of having a child with autism.
Significant associations were observed between subcategories of infection and intellectual disability and epilepsy, particularly those of a bacterial cause and from respiratory and genitourinary sites. Overall, any maternal infection during pregnancy was associated with a 43% increased risk of epilepsy, a 33% increased risk of intellectual disability, and an 8% increased risk of autism.
The exact mechanism of action between the maternal infection and adverse fetal neurodevelopmental outcomes is still unclear, Ms. Haber said at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology.
“Next, we are considering which specific [maternal] infections we should look at,” Ms. Haber said in an interview. “There is something about febrile infections, so we want to narrow that down and better characterize the outcomes from mild, moderate, severe infections.”
Ms. Haber reported having no relevant financial disclosures.
On Twitter @whitneymcknight
ANNAPOLIS, MD. – Febrile infections occurring in the second trimester appear to pose the greatest risk to the neurodevelopment of the fetus, a population based cohort study has shown.
In a review of 8,618,171 California births between January 1991 and December 2008, Ms. Hilary Haber, a third-year medical student at the University of California, Davis, and her coinvestigators found that maternal infections requiring hospitalizations during the second trimester were associated with a relative risk of 2.5 of having a child with epilepsy, a relative risk of 2.3 of having a child with an intellectual disability, and a relative risk of 1.2 of having a child with autism.
Significant associations were observed between subcategories of infection and intellectual disability and epilepsy, particularly those of a bacterial cause and from respiratory and genitourinary sites. Overall, any maternal infection during pregnancy was associated with a 43% increased risk of epilepsy, a 33% increased risk of intellectual disability, and an 8% increased risk of autism.
The exact mechanism of action between the maternal infection and adverse fetal neurodevelopmental outcomes is still unclear, Ms. Haber said at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology.
“Next, we are considering which specific [maternal] infections we should look at,” Ms. Haber said in an interview. “There is something about febrile infections, so we want to narrow that down and better characterize the outcomes from mild, moderate, severe infections.”
Ms. Haber reported having no relevant financial disclosures.
On Twitter @whitneymcknight
AT IDSOG
Key clinical point: Serious maternal infections in the second trimester pose an increased risk of having a child with epilepsy or intellectual disability.
Major finding: Maternal infections in the second trimester were associated with a relative risk of 2.5 of having a child with epilepsy.
Data source: Retrospective, population-based cohort study of more than 8 million births between 1991 and 2008.
Disclosures: Ms. Haber reported having no relevant financial disclosures.
Zika outbreak forces better history taking, tracking
ANNAPOLIS, MD. – The definition of taking a thorough travel history has expanded with the spread of Zika.
Physicians “need to focus not only on patients’ travel histories, but also the travel histories and future travel plans of our patients’ sexual partners,” Ilona T. Goldfarb, a perinatologist at Massachusetts General Hospital, Boston, said in an interview. “We cannot rely on our patients to just [offer] that they’ve been in the Caribbean. We have to ask them diligently, and at every visit.”
Dr. Goldfarb added that immigration is a risk for Zika exposure, and may be a barrier to accurate history taking. In these cases, travel history will need to be performed in the patient’s spoken language to ensure accuracy, Dr. Goldfarb said. To track and communicate Zika information, Dr. Goldfarb and her colleagues have developed a three-part response based on their experience with previous infectious disease emergencies:
1. Communication. The practice is in regular communication with the Centers for Disease Control and Prevention and the state public health department to ensure they are up to date on all guidelines.
2. Education. Dr. Goldfarb and her practice colleagues routinely brief each other and patients on any new information, including recommended testing and guidelines, as well as travel warnings.
3. Tracking. Clinicians use a tracking worksheet for every patient screened for potential Zika exposure, allowing them to prospectively and retrospectively review patients. This has already proven useful, Dr. Goldfarb said, when the CDC changed its guidance around testing of asymptomatic patients.
In a presentation at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology, Dr. Goldfarb presented the data that she and her colleagues have collected so far on patients with Zika exposure.
As of Aug. 10, 2016, the practice had screened 142 women for Zika virus exposure since January 2016. More than 80% of the exposure came from travel to Zika-endemic areas. There have been few cases of exposure reported through sex, but Dr. Goldfarb said she thinks this type of exposure has been underreported because the link between infection and sex was not known until more recently.
Of the patients screened, 87% were appropriate candidates for Zika virus serum testing under CDC guidelines. There have been four positive serum tests for Zika exposure in Dr. Goldfarb’s patients so far.
In the one live birth, the newborn showed no visible signs of abnormalities. Testing revealed Zika virus RNA in the placenta, but not in the cord blood. The other three pregnancies were either terminated or associated with miscarriages. Again, Zika was detected in the placentas, but not in the fetuses.
Testing protocols have been a moving target since the outbreak began, according to Dr. Goldfarb. Some patients who call or are screened for possible exposure “are not actually eligible for testing because of the time frame or location of travel.”
To make sure that appropriate testing is being performed, Dr. Goldfarb advised designating an in-practice “Zika expert.” In her own practice, Dr. Goldfarb and one other colleague handle all Zika screening and inquiries from patients and colleagues. “This has greatly improved our efficiency and the experience for the patients,” she said in an interview.
The Massachusetts Department of Public Health is piloting a program with Dr. Goldfarb’s practice to determine if using the “designated expert” approach will improve laboratory wait times, compared with the standard protocol of having clinicians obtain approval from a state epidemiologist before sending patient serum samples for testing.
It has taken from 2 to 68 days to receive test results from the state lab, although a period of 17 days is typical, Dr. Goldfarb reported. The process has improved since last March when state health officials ramped up their capacity, she said.
As of Aug. 10, Dr. Goldfarb’s practice has performed 107 ultrasounds for patients with suspected Zika virus, averaging 3 per patient. Across all ultrasounds, there were three abnormalities, including one case of bilateral ventriculomegaly. Earlier in that pregnancy, the patient had tested negative for Zika on real-time reverse transcription polymerase chain reaction testing, which simultaneously screens for dengue, chikungunya, and Zika. Serum testing was also negative for Zika in the two other pregnancies with fetal abnormalities.
Dr. Goldfarb said she couldn’t quantify how much time is being spent on Zika screening and counseling since that is not being tracked, but she estimated that her practice takes between three and five calls or questions per day regarding the virus.
On Twitter @whitneymcknight
ANNAPOLIS, MD. – The definition of taking a thorough travel history has expanded with the spread of Zika.
Physicians “need to focus not only on patients’ travel histories, but also the travel histories and future travel plans of our patients’ sexual partners,” Ilona T. Goldfarb, a perinatologist at Massachusetts General Hospital, Boston, said in an interview. “We cannot rely on our patients to just [offer] that they’ve been in the Caribbean. We have to ask them diligently, and at every visit.”
Dr. Goldfarb added that immigration is a risk for Zika exposure, and may be a barrier to accurate history taking. In these cases, travel history will need to be performed in the patient’s spoken language to ensure accuracy, Dr. Goldfarb said. To track and communicate Zika information, Dr. Goldfarb and her colleagues have developed a three-part response based on their experience with previous infectious disease emergencies:
1. Communication. The practice is in regular communication with the Centers for Disease Control and Prevention and the state public health department to ensure they are up to date on all guidelines.
2. Education. Dr. Goldfarb and her practice colleagues routinely brief each other and patients on any new information, including recommended testing and guidelines, as well as travel warnings.
3. Tracking. Clinicians use a tracking worksheet for every patient screened for potential Zika exposure, allowing them to prospectively and retrospectively review patients. This has already proven useful, Dr. Goldfarb said, when the CDC changed its guidance around testing of asymptomatic patients.
In a presentation at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology, Dr. Goldfarb presented the data that she and her colleagues have collected so far on patients with Zika exposure.
As of Aug. 10, 2016, the practice had screened 142 women for Zika virus exposure since January 2016. More than 80% of the exposure came from travel to Zika-endemic areas. There have been few cases of exposure reported through sex, but Dr. Goldfarb said she thinks this type of exposure has been underreported because the link between infection and sex was not known until more recently.
Of the patients screened, 87% were appropriate candidates for Zika virus serum testing under CDC guidelines. There have been four positive serum tests for Zika exposure in Dr. Goldfarb’s patients so far.
In the one live birth, the newborn showed no visible signs of abnormalities. Testing revealed Zika virus RNA in the placenta, but not in the cord blood. The other three pregnancies were either terminated or associated with miscarriages. Again, Zika was detected in the placentas, but not in the fetuses.
Testing protocols have been a moving target since the outbreak began, according to Dr. Goldfarb. Some patients who call or are screened for possible exposure “are not actually eligible for testing because of the time frame or location of travel.”
To make sure that appropriate testing is being performed, Dr. Goldfarb advised designating an in-practice “Zika expert.” In her own practice, Dr. Goldfarb and one other colleague handle all Zika screening and inquiries from patients and colleagues. “This has greatly improved our efficiency and the experience for the patients,” she said in an interview.
The Massachusetts Department of Public Health is piloting a program with Dr. Goldfarb’s practice to determine if using the “designated expert” approach will improve laboratory wait times, compared with the standard protocol of having clinicians obtain approval from a state epidemiologist before sending patient serum samples for testing.
It has taken from 2 to 68 days to receive test results from the state lab, although a period of 17 days is typical, Dr. Goldfarb reported. The process has improved since last March when state health officials ramped up their capacity, she said.
As of Aug. 10, Dr. Goldfarb’s practice has performed 107 ultrasounds for patients with suspected Zika virus, averaging 3 per patient. Across all ultrasounds, there were three abnormalities, including one case of bilateral ventriculomegaly. Earlier in that pregnancy, the patient had tested negative for Zika on real-time reverse transcription polymerase chain reaction testing, which simultaneously screens for dengue, chikungunya, and Zika. Serum testing was also negative for Zika in the two other pregnancies with fetal abnormalities.
Dr. Goldfarb said she couldn’t quantify how much time is being spent on Zika screening and counseling since that is not being tracked, but she estimated that her practice takes between three and five calls or questions per day regarding the virus.
On Twitter @whitneymcknight
ANNAPOLIS, MD. – The definition of taking a thorough travel history has expanded with the spread of Zika.
Physicians “need to focus not only on patients’ travel histories, but also the travel histories and future travel plans of our patients’ sexual partners,” Ilona T. Goldfarb, a perinatologist at Massachusetts General Hospital, Boston, said in an interview. “We cannot rely on our patients to just [offer] that they’ve been in the Caribbean. We have to ask them diligently, and at every visit.”
Dr. Goldfarb added that immigration is a risk for Zika exposure, and may be a barrier to accurate history taking. In these cases, travel history will need to be performed in the patient’s spoken language to ensure accuracy, Dr. Goldfarb said. To track and communicate Zika information, Dr. Goldfarb and her colleagues have developed a three-part response based on their experience with previous infectious disease emergencies:
1. Communication. The practice is in regular communication with the Centers for Disease Control and Prevention and the state public health department to ensure they are up to date on all guidelines.
2. Education. Dr. Goldfarb and her practice colleagues routinely brief each other and patients on any new information, including recommended testing and guidelines, as well as travel warnings.
3. Tracking. Clinicians use a tracking worksheet for every patient screened for potential Zika exposure, allowing them to prospectively and retrospectively review patients. This has already proven useful, Dr. Goldfarb said, when the CDC changed its guidance around testing of asymptomatic patients.
In a presentation at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology, Dr. Goldfarb presented the data that she and her colleagues have collected so far on patients with Zika exposure.
As of Aug. 10, 2016, the practice had screened 142 women for Zika virus exposure since January 2016. More than 80% of the exposure came from travel to Zika-endemic areas. There have been few cases of exposure reported through sex, but Dr. Goldfarb said she thinks this type of exposure has been underreported because the link between infection and sex was not known until more recently.
Of the patients screened, 87% were appropriate candidates for Zika virus serum testing under CDC guidelines. There have been four positive serum tests for Zika exposure in Dr. Goldfarb’s patients so far.
In the one live birth, the newborn showed no visible signs of abnormalities. Testing revealed Zika virus RNA in the placenta, but not in the cord blood. The other three pregnancies were either terminated or associated with miscarriages. Again, Zika was detected in the placentas, but not in the fetuses.
Testing protocols have been a moving target since the outbreak began, according to Dr. Goldfarb. Some patients who call or are screened for possible exposure “are not actually eligible for testing because of the time frame or location of travel.”
To make sure that appropriate testing is being performed, Dr. Goldfarb advised designating an in-practice “Zika expert.” In her own practice, Dr. Goldfarb and one other colleague handle all Zika screening and inquiries from patients and colleagues. “This has greatly improved our efficiency and the experience for the patients,” she said in an interview.
The Massachusetts Department of Public Health is piloting a program with Dr. Goldfarb’s practice to determine if using the “designated expert” approach will improve laboratory wait times, compared with the standard protocol of having clinicians obtain approval from a state epidemiologist before sending patient serum samples for testing.
It has taken from 2 to 68 days to receive test results from the state lab, although a period of 17 days is typical, Dr. Goldfarb reported. The process has improved since last March when state health officials ramped up their capacity, she said.
As of Aug. 10, Dr. Goldfarb’s practice has performed 107 ultrasounds for patients with suspected Zika virus, averaging 3 per patient. Across all ultrasounds, there were three abnormalities, including one case of bilateral ventriculomegaly. Earlier in that pregnancy, the patient had tested negative for Zika on real-time reverse transcription polymerase chain reaction testing, which simultaneously screens for dengue, chikungunya, and Zika. Serum testing was also negative for Zika in the two other pregnancies with fetal abnormalities.
Dr. Goldfarb said she couldn’t quantify how much time is being spent on Zika screening and counseling since that is not being tracked, but she estimated that her practice takes between three and five calls or questions per day regarding the virus.
On Twitter @whitneymcknight
EXPERT ANALYSIS FROM IDSOG
Zika virus pits pregnant women against time, knowledge gaps
ANNAPOLIS, MD. – The scramble to learn exactly how and when after infection the Zika virus affects the developing fetus has put pregnant women at the center of an unprecedented infectious disease emergency response.
“It’s the most complicated infectious disease response we’ve ever done,” Dana Meaney-Delman, MD, of the Centers for Disease Control and Prevention, told an audience at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology. “It’s also the first time an emergency response team has included an ob.gyn.”
Although research into Zika virus is happening at breakneck speed, every finding seems to lead to still more questions. “It’s hard to keep up,” said Dr. Meaney-Delman, who is a Clinical Deputy on the Pregnancy and Birth Defects Task Force, part of the CDC’s Zika virus response.
What is known
What is known is that Zika virus is primarily vector-borne, either manifesting as a mild illness or remaining subclinical. The virus is also communicable through male-to-female sex, female-to-female sex, blood donation, and organ transplantation. Once infected, one is immune; if symptomatic, the presentation clears within a couple of weeks. If a woman is infected during pregnancy, it can be transmitted to the developing fetus, including at the time of birth, according to Dr. Meaney-Delman.
“We know transmission can occur in any trimester. We’ve seen it in the placenta, in amniotic fluid, in the brain, as well as in the brains of infants who have died,” she said.
Whether the virus poses a risk to the fetus around the time of conception is not clear, but Dr. Meaney-Delman said that since other infections such as rubella and cytomegalovirus do pose a risk, the CDC is issuing Zika guidance accordingly.
Despite an initial theory that pregnant women were more susceptible to Zika infection, there is no evidence to date confirming this, but “the combination of mosquitoes and sexual transmission really puts a woman of reproductive age at risk,” said Catherine Y. Spong, MD, who also spoke during the meeting. Dr. Spong is acting director of the National Institute of Child Health and Human Development, part of the National Institutes of Health.
Based on data derived from other flaviviruses, the “good news” is that infected nonpregnant women who later want to conceive do not have a higher risk of bearing a child with Zika-related complications, according to Dr. Meaney-Delman.
Abnormalities seen and unseen
During the initial stages of the Zika outbreak in Brazil, the spiking rate of babies born with microcephaly attracted the most attention; yet it is now apparent that children were also born with a growing list of other Zika-associated pregnancy outcomes that likely were missed at the time, according to Dr. Spong.
“That’s not to say that a child that doesn’t have microcephaly does or doesn’t have some of these other complications. We don’t know; they weren’t studied because they didn’t have the microcephaly,” Dr Spong said. “To get the data right, you need to follow all the children.”
Brain abnormalities such as ventriculomegaly and intracranial calcifications, as well as a range of growth abnormalities, miscarriage, and stillbirth are increasingly associated with infants born to infected women. Data is also beginning to link Zika virus to limb abnormalities, hypertonia, hearing loss, damage to the eyes and central nervous system, and seizures.
The World Health Organization has also noted the involvement of the cardiac, genitourinary, and digestive systems in babies born to infected mothers in Panama and Colombia. “The caveat [to these data], is that all these women were symptomatic,” Dr. Spong said, noting that in Brazil, where the outbreak was first documented, 80% of the infected pregnant women were asymptomatic during the pregnancy.
“Just because the mother has no symptoms, she’s fine? That doesn’t make any sense to me,” Dr. Spong said. “We know that infections in pregnancy can result in long-term outcomes in kids that you don’t have the ability to diagnose at birth. We need to be cognizant of this and we need to study it.”
Although initial theories were that viremia in symptomatic women was likely higher, thus imparting a higher risk of infection in their fetus, Dr. Meaney-Delman said the number of asymptomatic women whose fetuses are affected has debunked this line of thinking.
Risk of infection during pregnancy
As to what the actual risk of Zika virus infection is during pregnancy, “honestly we don’t know,” said Dr. Spong. “There are modeling estimates that [it’s] between 1% and 13% in a first trimester infection, but we don’t have the hard and fast data.”
The Zika in Infants and Pregnancy (ZIP) study, recently launched by the NIH, will provide a prospective look at birth outcomes in 10,000 women aged 15 years and older who will be followed throughout their pregnancies to determine if they become infected with Zika virus, and if so, how infection impacts birth outcomes.
The international, multi-site study will help clarify the timing of risk, Dr. Spong said, and is intended to elucidate pregnancy risks in symptomatic vs. asymptomatic women. The study will also help indicate whether nutritional, socioeconomic status, and other cofactors such as Dengue infection are implicated. Once born, all children in the study will be observed for a year. “Even if they have no abnormalities, after birth there could be developmental delays, or more subtle consequences later on in the child’s life,” Dr. Meaney-Delman said.
Meanwhile, researchers are attempting to map how varying levels of viremia affect transmission. Zika virus has been found in semen after 90 days in at least two studies, “and we don’t know if Zika can be transmitted through other bodily fluids,” Dr. Spong said.
Surveillance data from the CDC’s Zika Pregnancy Registry has shown viremia in symptomatic women can last up to 46 days after onset of symptoms. In at least one asymptomatic pregnant woman, viremia was detected 53 days after exposure. Another study found prolonged viremia – 10 weeks – in a patient who had Zika infection in her first trimester; imaging showed the fetus was developing normally until week 20, when signs of severe brain abnormalities were detected.
The emerging picture of Zika’s potential for prolonged viremia has prompted the CDC to recommend clinicians use reverse transcription–polymerase chain reaction (RT-PCR) testing rather than serologic testing, as it is more sensitive and helps rule out other flavivirus infections, which require different management, Dr. Meaney-Delman said.
Potential mechanisms of action
“It’s clear that the virus does directly infect human cortical neural progenitor cells with very high efficiency, and in doing so, stunts their growth, dysregulates transcription, and causes cell death,” Dr. Spong said.
Researchers have also found that Zika replicates in subgroups of trophoblasts and endothelial cells, and in primary human placental macrophages, resulting in vascular damage and growth restriction. Other research suggests the virus spreads from basal and parietal decidua to chorionic villi and amniochorionic membranes, leading to the theory that uterine-placental suppression of the viral entry cofactor TIM1 could stop transmission to the fetus.
Prevention and management
CDC officials expect the current outbreak to mimic past flavivirus outbreaks which were contained locally in portions of the South and U.S. territories, Dr. Meaney-Delman said. Still, she emphasized that clinicians should screen patients, regardless of location. “Each pregnant women should be assessed for [vector] exposure, travel, and sexual exposure and asked about symptoms consistent with Zika virus,” Dr. Meaney-Delman said.
She also emphasized the importance of patients consistently using insect repellent and using condoms during pregnancy, as Zika has been detected in semen for as long as 6 months. “It’s been very hard to invoke this behavioral change in women, but it’s very effective.”
The CDC continues to update guidance, including how to evaluate newborns for Zika-related defects.
As for what resources might be needed in future to help affected families, in an interview Dr. Meaney-Delman said that depends on information still unknown. “Zika is a public health concern that we should be factoring in long term, but what we do about it will depend upon the outcomes,” she said. “If there are children that are born normal but who have lab evidence of Zika, then we will probably not do much. I don’t think we have a projection yet.”
On Twitter @whitneymcknight
ANNAPOLIS, MD. – The scramble to learn exactly how and when after infection the Zika virus affects the developing fetus has put pregnant women at the center of an unprecedented infectious disease emergency response.
“It’s the most complicated infectious disease response we’ve ever done,” Dana Meaney-Delman, MD, of the Centers for Disease Control and Prevention, told an audience at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology. “It’s also the first time an emergency response team has included an ob.gyn.”
Although research into Zika virus is happening at breakneck speed, every finding seems to lead to still more questions. “It’s hard to keep up,” said Dr. Meaney-Delman, who is a Clinical Deputy on the Pregnancy and Birth Defects Task Force, part of the CDC’s Zika virus response.
What is known
What is known is that Zika virus is primarily vector-borne, either manifesting as a mild illness or remaining subclinical. The virus is also communicable through male-to-female sex, female-to-female sex, blood donation, and organ transplantation. Once infected, one is immune; if symptomatic, the presentation clears within a couple of weeks. If a woman is infected during pregnancy, it can be transmitted to the developing fetus, including at the time of birth, according to Dr. Meaney-Delman.
“We know transmission can occur in any trimester. We’ve seen it in the placenta, in amniotic fluid, in the brain, as well as in the brains of infants who have died,” she said.
Whether the virus poses a risk to the fetus around the time of conception is not clear, but Dr. Meaney-Delman said that since other infections such as rubella and cytomegalovirus do pose a risk, the CDC is issuing Zika guidance accordingly.
Despite an initial theory that pregnant women were more susceptible to Zika infection, there is no evidence to date confirming this, but “the combination of mosquitoes and sexual transmission really puts a woman of reproductive age at risk,” said Catherine Y. Spong, MD, who also spoke during the meeting. Dr. Spong is acting director of the National Institute of Child Health and Human Development, part of the National Institutes of Health.
Based on data derived from other flaviviruses, the “good news” is that infected nonpregnant women who later want to conceive do not have a higher risk of bearing a child with Zika-related complications, according to Dr. Meaney-Delman.
Abnormalities seen and unseen
During the initial stages of the Zika outbreak in Brazil, the spiking rate of babies born with microcephaly attracted the most attention; yet it is now apparent that children were also born with a growing list of other Zika-associated pregnancy outcomes that likely were missed at the time, according to Dr. Spong.
“That’s not to say that a child that doesn’t have microcephaly does or doesn’t have some of these other complications. We don’t know; they weren’t studied because they didn’t have the microcephaly,” Dr Spong said. “To get the data right, you need to follow all the children.”
Brain abnormalities such as ventriculomegaly and intracranial calcifications, as well as a range of growth abnormalities, miscarriage, and stillbirth are increasingly associated with infants born to infected women. Data is also beginning to link Zika virus to limb abnormalities, hypertonia, hearing loss, damage to the eyes and central nervous system, and seizures.
The World Health Organization has also noted the involvement of the cardiac, genitourinary, and digestive systems in babies born to infected mothers in Panama and Colombia. “The caveat [to these data], is that all these women were symptomatic,” Dr. Spong said, noting that in Brazil, where the outbreak was first documented, 80% of the infected pregnant women were asymptomatic during the pregnancy.
“Just because the mother has no symptoms, she’s fine? That doesn’t make any sense to me,” Dr. Spong said. “We know that infections in pregnancy can result in long-term outcomes in kids that you don’t have the ability to diagnose at birth. We need to be cognizant of this and we need to study it.”
Although initial theories were that viremia in symptomatic women was likely higher, thus imparting a higher risk of infection in their fetus, Dr. Meaney-Delman said the number of asymptomatic women whose fetuses are affected has debunked this line of thinking.
Risk of infection during pregnancy
As to what the actual risk of Zika virus infection is during pregnancy, “honestly we don’t know,” said Dr. Spong. “There are modeling estimates that [it’s] between 1% and 13% in a first trimester infection, but we don’t have the hard and fast data.”
The Zika in Infants and Pregnancy (ZIP) study, recently launched by the NIH, will provide a prospective look at birth outcomes in 10,000 women aged 15 years and older who will be followed throughout their pregnancies to determine if they become infected with Zika virus, and if so, how infection impacts birth outcomes.
The international, multi-site study will help clarify the timing of risk, Dr. Spong said, and is intended to elucidate pregnancy risks in symptomatic vs. asymptomatic women. The study will also help indicate whether nutritional, socioeconomic status, and other cofactors such as Dengue infection are implicated. Once born, all children in the study will be observed for a year. “Even if they have no abnormalities, after birth there could be developmental delays, or more subtle consequences later on in the child’s life,” Dr. Meaney-Delman said.
Meanwhile, researchers are attempting to map how varying levels of viremia affect transmission. Zika virus has been found in semen after 90 days in at least two studies, “and we don’t know if Zika can be transmitted through other bodily fluids,” Dr. Spong said.
Surveillance data from the CDC’s Zika Pregnancy Registry has shown viremia in symptomatic women can last up to 46 days after onset of symptoms. In at least one asymptomatic pregnant woman, viremia was detected 53 days after exposure. Another study found prolonged viremia – 10 weeks – in a patient who had Zika infection in her first trimester; imaging showed the fetus was developing normally until week 20, when signs of severe brain abnormalities were detected.
The emerging picture of Zika’s potential for prolonged viremia has prompted the CDC to recommend clinicians use reverse transcription–polymerase chain reaction (RT-PCR) testing rather than serologic testing, as it is more sensitive and helps rule out other flavivirus infections, which require different management, Dr. Meaney-Delman said.
Potential mechanisms of action
“It’s clear that the virus does directly infect human cortical neural progenitor cells with very high efficiency, and in doing so, stunts their growth, dysregulates transcription, and causes cell death,” Dr. Spong said.
Researchers have also found that Zika replicates in subgroups of trophoblasts and endothelial cells, and in primary human placental macrophages, resulting in vascular damage and growth restriction. Other research suggests the virus spreads from basal and parietal decidua to chorionic villi and amniochorionic membranes, leading to the theory that uterine-placental suppression of the viral entry cofactor TIM1 could stop transmission to the fetus.
Prevention and management
CDC officials expect the current outbreak to mimic past flavivirus outbreaks which were contained locally in portions of the South and U.S. territories, Dr. Meaney-Delman said. Still, she emphasized that clinicians should screen patients, regardless of location. “Each pregnant women should be assessed for [vector] exposure, travel, and sexual exposure and asked about symptoms consistent with Zika virus,” Dr. Meaney-Delman said.
She also emphasized the importance of patients consistently using insect repellent and using condoms during pregnancy, as Zika has been detected in semen for as long as 6 months. “It’s been very hard to invoke this behavioral change in women, but it’s very effective.”
The CDC continues to update guidance, including how to evaluate newborns for Zika-related defects.
As for what resources might be needed in future to help affected families, in an interview Dr. Meaney-Delman said that depends on information still unknown. “Zika is a public health concern that we should be factoring in long term, but what we do about it will depend upon the outcomes,” she said. “If there are children that are born normal but who have lab evidence of Zika, then we will probably not do much. I don’t think we have a projection yet.”
On Twitter @whitneymcknight
ANNAPOLIS, MD. – The scramble to learn exactly how and when after infection the Zika virus affects the developing fetus has put pregnant women at the center of an unprecedented infectious disease emergency response.
“It’s the most complicated infectious disease response we’ve ever done,” Dana Meaney-Delman, MD, of the Centers for Disease Control and Prevention, told an audience at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology. “It’s also the first time an emergency response team has included an ob.gyn.”
Although research into Zika virus is happening at breakneck speed, every finding seems to lead to still more questions. “It’s hard to keep up,” said Dr. Meaney-Delman, who is a Clinical Deputy on the Pregnancy and Birth Defects Task Force, part of the CDC’s Zika virus response.
What is known
What is known is that Zika virus is primarily vector-borne, either manifesting as a mild illness or remaining subclinical. The virus is also communicable through male-to-female sex, female-to-female sex, blood donation, and organ transplantation. Once infected, one is immune; if symptomatic, the presentation clears within a couple of weeks. If a woman is infected during pregnancy, it can be transmitted to the developing fetus, including at the time of birth, according to Dr. Meaney-Delman.
“We know transmission can occur in any trimester. We’ve seen it in the placenta, in amniotic fluid, in the brain, as well as in the brains of infants who have died,” she said.
Whether the virus poses a risk to the fetus around the time of conception is not clear, but Dr. Meaney-Delman said that since other infections such as rubella and cytomegalovirus do pose a risk, the CDC is issuing Zika guidance accordingly.
Despite an initial theory that pregnant women were more susceptible to Zika infection, there is no evidence to date confirming this, but “the combination of mosquitoes and sexual transmission really puts a woman of reproductive age at risk,” said Catherine Y. Spong, MD, who also spoke during the meeting. Dr. Spong is acting director of the National Institute of Child Health and Human Development, part of the National Institutes of Health.
Based on data derived from other flaviviruses, the “good news” is that infected nonpregnant women who later want to conceive do not have a higher risk of bearing a child with Zika-related complications, according to Dr. Meaney-Delman.
Abnormalities seen and unseen
During the initial stages of the Zika outbreak in Brazil, the spiking rate of babies born with microcephaly attracted the most attention; yet it is now apparent that children were also born with a growing list of other Zika-associated pregnancy outcomes that likely were missed at the time, according to Dr. Spong.
“That’s not to say that a child that doesn’t have microcephaly does or doesn’t have some of these other complications. We don’t know; they weren’t studied because they didn’t have the microcephaly,” Dr Spong said. “To get the data right, you need to follow all the children.”
Brain abnormalities such as ventriculomegaly and intracranial calcifications, as well as a range of growth abnormalities, miscarriage, and stillbirth are increasingly associated with infants born to infected women. Data is also beginning to link Zika virus to limb abnormalities, hypertonia, hearing loss, damage to the eyes and central nervous system, and seizures.
The World Health Organization has also noted the involvement of the cardiac, genitourinary, and digestive systems in babies born to infected mothers in Panama and Colombia. “The caveat [to these data], is that all these women were symptomatic,” Dr. Spong said, noting that in Brazil, where the outbreak was first documented, 80% of the infected pregnant women were asymptomatic during the pregnancy.
“Just because the mother has no symptoms, she’s fine? That doesn’t make any sense to me,” Dr. Spong said. “We know that infections in pregnancy can result in long-term outcomes in kids that you don’t have the ability to diagnose at birth. We need to be cognizant of this and we need to study it.”
Although initial theories were that viremia in symptomatic women was likely higher, thus imparting a higher risk of infection in their fetus, Dr. Meaney-Delman said the number of asymptomatic women whose fetuses are affected has debunked this line of thinking.
Risk of infection during pregnancy
As to what the actual risk of Zika virus infection is during pregnancy, “honestly we don’t know,” said Dr. Spong. “There are modeling estimates that [it’s] between 1% and 13% in a first trimester infection, but we don’t have the hard and fast data.”
The Zika in Infants and Pregnancy (ZIP) study, recently launched by the NIH, will provide a prospective look at birth outcomes in 10,000 women aged 15 years and older who will be followed throughout their pregnancies to determine if they become infected with Zika virus, and if so, how infection impacts birth outcomes.
The international, multi-site study will help clarify the timing of risk, Dr. Spong said, and is intended to elucidate pregnancy risks in symptomatic vs. asymptomatic women. The study will also help indicate whether nutritional, socioeconomic status, and other cofactors such as Dengue infection are implicated. Once born, all children in the study will be observed for a year. “Even if they have no abnormalities, after birth there could be developmental delays, or more subtle consequences later on in the child’s life,” Dr. Meaney-Delman said.
Meanwhile, researchers are attempting to map how varying levels of viremia affect transmission. Zika virus has been found in semen after 90 days in at least two studies, “and we don’t know if Zika can be transmitted through other bodily fluids,” Dr. Spong said.
Surveillance data from the CDC’s Zika Pregnancy Registry has shown viremia in symptomatic women can last up to 46 days after onset of symptoms. In at least one asymptomatic pregnant woman, viremia was detected 53 days after exposure. Another study found prolonged viremia – 10 weeks – in a patient who had Zika infection in her first trimester; imaging showed the fetus was developing normally until week 20, when signs of severe brain abnormalities were detected.
The emerging picture of Zika’s potential for prolonged viremia has prompted the CDC to recommend clinicians use reverse transcription–polymerase chain reaction (RT-PCR) testing rather than serologic testing, as it is more sensitive and helps rule out other flavivirus infections, which require different management, Dr. Meaney-Delman said.
Potential mechanisms of action
“It’s clear that the virus does directly infect human cortical neural progenitor cells with very high efficiency, and in doing so, stunts their growth, dysregulates transcription, and causes cell death,” Dr. Spong said.
Researchers have also found that Zika replicates in subgroups of trophoblasts and endothelial cells, and in primary human placental macrophages, resulting in vascular damage and growth restriction. Other research suggests the virus spreads from basal and parietal decidua to chorionic villi and amniochorionic membranes, leading to the theory that uterine-placental suppression of the viral entry cofactor TIM1 could stop transmission to the fetus.
Prevention and management
CDC officials expect the current outbreak to mimic past flavivirus outbreaks which were contained locally in portions of the South and U.S. territories, Dr. Meaney-Delman said. Still, she emphasized that clinicians should screen patients, regardless of location. “Each pregnant women should be assessed for [vector] exposure, travel, and sexual exposure and asked about symptoms consistent with Zika virus,” Dr. Meaney-Delman said.
She also emphasized the importance of patients consistently using insect repellent and using condoms during pregnancy, as Zika has been detected in semen for as long as 6 months. “It’s been very hard to invoke this behavioral change in women, but it’s very effective.”
The CDC continues to update guidance, including how to evaluate newborns for Zika-related defects.
As for what resources might be needed in future to help affected families, in an interview Dr. Meaney-Delman said that depends on information still unknown. “Zika is a public health concern that we should be factoring in long term, but what we do about it will depend upon the outcomes,” she said. “If there are children that are born normal but who have lab evidence of Zika, then we will probably not do much. I don’t think we have a projection yet.”
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