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Replicative Zika RNA found in brain and placental tissue

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Fri, 01/18/2019 - 16:25

 

U.S.-based researchers have isolated replicative Zika virus RNA from the brain tissue of infants with microcephaly, and the placenta and fetal tissues from women suspected of being infected with Zika virus during pregnancy.

In a paper published online in Emerging Infectious Diseases, Julu Bhatnagar, PhD, of the Infectious Diseases Pathology Branch at the Center for Emerging and Zoonotic Infectious Diseases in Atlanta, and her coauthors reported a case series in 52 patients – 8 infants with microcephaly who died and 44 women thought to have been infected with Zika virus during pregnancy – using Zika virus reverse transcription PCR and in situ hybridization assay to detect the virus.

copyright Devonyu/Thinkstock
While Zika virus antigens have previously been detected in placentas and in fetal or neonatal brains, this does not necessarily indicate virus replication, the authors wrote (Emerg Infect Dis. 2016 Dec 14. doi: 10.3201/eid2303.161499).

“Nevertheless, localization of replicating Zika virus RNA directly in the tissues of patients with congenital and pregnancy-associated infections is critical for identifying cellular targets of Zika virus infection and virus persistence in various tissues and for further investigating the mechanism of Zika virus intrauterine transmission,” Dr. Bhatnagar said.

Using RT-PCR, the researchers were able to isolate Zika virus RNA from 32 (62%) of the case-patients – all 8 infants with microcephaly who died, and 24 women.

There were no major clinical differences between the women who tested positive for Zika virus with RT-PCR and those who tested negative; the most common symptoms in both groups were rash, fever, arthralgia, headache and conjunctivitis.

Among women who had an adverse pregnancy or birth outcome, 24 (75%) tested positive for Zika virus via RT-PCR, compared to 8 (36%) women with live-born healthy infants (P = .0082).

Symptom onset during the first trimester was associated with a significantly higher risk of adverse pregnancy and birth outcomes. Of the 24 women with positive RT-PCR results and adverse pregnancy outcomes, 23 had symptom onset during the first trimester, while all 8 patients with positive RT-PCR results but healthy infants had symptom onset in the third trimester (P less than .0001).

There were eight cases of infants with microcephaly who died within a few minutes to 2 months after birth, and five women who delivered live infants with microcephaly who survived.

All but one of these tested positive for Zika virus by RT-PCR, either in brain tissue or placental/fetal tissue, and all the women experienced symptom onset during the first trimester. Zika virus was not detected in other tissues from the infants.

Researchers also found that the levels of Zika virus RNA in the brain tissues of the infants who had microcephaly and died were around 1,200-fold higher than the levels observed in second or third trimester or full-term placentas.

Using in situ hybridization assays, researchers found Zika virus RNA in half of the tissues of the 32 case-patients who tested positive with RT-PCR.

“Zika virus replicative RNA, detected by using sense probe, was observed in the neural cells, neurons, and degenerating glial cells within the cerebral cortex of the brain,” the authors wrote.

Zika virus genomic and replicative RNA also was found in the placental chorionic villi – predominantly in the Hofbauer cells – in 9 (75%) of the 12 women with positive RT-PCR results who had experienced an adverse pregnancy outcome during the first or second trimester. The authors said this indicated the possibility that the Hofbauer cells may play a role in disseminating or transferring the virus to the fetal brain.

“This article highlights the value of tissue analysis to expand opportunities to diagnose Zika virus congenital and pregnancy-associated infections and to enhance the understanding of mechanism of Zika virus intrauterine transmission and pathogenesis,” the authors wrote. “In addition, the tissue-based RT-PCRs extend the time frame for Zika virus detection and particularly help to establish a diagnosis retrospectively, enabling pregnant women and their health care providers to identify the cause of severe microcephaly or fetal loss.”

No conflicts of interest were declared.

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U.S.-based researchers have isolated replicative Zika virus RNA from the brain tissue of infants with microcephaly, and the placenta and fetal tissues from women suspected of being infected with Zika virus during pregnancy.

In a paper published online in Emerging Infectious Diseases, Julu Bhatnagar, PhD, of the Infectious Diseases Pathology Branch at the Center for Emerging and Zoonotic Infectious Diseases in Atlanta, and her coauthors reported a case series in 52 patients – 8 infants with microcephaly who died and 44 women thought to have been infected with Zika virus during pregnancy – using Zika virus reverse transcription PCR and in situ hybridization assay to detect the virus.

copyright Devonyu/Thinkstock
While Zika virus antigens have previously been detected in placentas and in fetal or neonatal brains, this does not necessarily indicate virus replication, the authors wrote (Emerg Infect Dis. 2016 Dec 14. doi: 10.3201/eid2303.161499).

“Nevertheless, localization of replicating Zika virus RNA directly in the tissues of patients with congenital and pregnancy-associated infections is critical for identifying cellular targets of Zika virus infection and virus persistence in various tissues and for further investigating the mechanism of Zika virus intrauterine transmission,” Dr. Bhatnagar said.

Using RT-PCR, the researchers were able to isolate Zika virus RNA from 32 (62%) of the case-patients – all 8 infants with microcephaly who died, and 24 women.

There were no major clinical differences between the women who tested positive for Zika virus with RT-PCR and those who tested negative; the most common symptoms in both groups were rash, fever, arthralgia, headache and conjunctivitis.

Among women who had an adverse pregnancy or birth outcome, 24 (75%) tested positive for Zika virus via RT-PCR, compared to 8 (36%) women with live-born healthy infants (P = .0082).

Symptom onset during the first trimester was associated with a significantly higher risk of adverse pregnancy and birth outcomes. Of the 24 women with positive RT-PCR results and adverse pregnancy outcomes, 23 had symptom onset during the first trimester, while all 8 patients with positive RT-PCR results but healthy infants had symptom onset in the third trimester (P less than .0001).

There were eight cases of infants with microcephaly who died within a few minutes to 2 months after birth, and five women who delivered live infants with microcephaly who survived.

All but one of these tested positive for Zika virus by RT-PCR, either in brain tissue or placental/fetal tissue, and all the women experienced symptom onset during the first trimester. Zika virus was not detected in other tissues from the infants.

Researchers also found that the levels of Zika virus RNA in the brain tissues of the infants who had microcephaly and died were around 1,200-fold higher than the levels observed in second or third trimester or full-term placentas.

Using in situ hybridization assays, researchers found Zika virus RNA in half of the tissues of the 32 case-patients who tested positive with RT-PCR.

“Zika virus replicative RNA, detected by using sense probe, was observed in the neural cells, neurons, and degenerating glial cells within the cerebral cortex of the brain,” the authors wrote.

Zika virus genomic and replicative RNA also was found in the placental chorionic villi – predominantly in the Hofbauer cells – in 9 (75%) of the 12 women with positive RT-PCR results who had experienced an adverse pregnancy outcome during the first or second trimester. The authors said this indicated the possibility that the Hofbauer cells may play a role in disseminating or transferring the virus to the fetal brain.

“This article highlights the value of tissue analysis to expand opportunities to diagnose Zika virus congenital and pregnancy-associated infections and to enhance the understanding of mechanism of Zika virus intrauterine transmission and pathogenesis,” the authors wrote. “In addition, the tissue-based RT-PCRs extend the time frame for Zika virus detection and particularly help to establish a diagnosis retrospectively, enabling pregnant women and their health care providers to identify the cause of severe microcephaly or fetal loss.”

No conflicts of interest were declared.

 

U.S.-based researchers have isolated replicative Zika virus RNA from the brain tissue of infants with microcephaly, and the placenta and fetal tissues from women suspected of being infected with Zika virus during pregnancy.

In a paper published online in Emerging Infectious Diseases, Julu Bhatnagar, PhD, of the Infectious Diseases Pathology Branch at the Center for Emerging and Zoonotic Infectious Diseases in Atlanta, and her coauthors reported a case series in 52 patients – 8 infants with microcephaly who died and 44 women thought to have been infected with Zika virus during pregnancy – using Zika virus reverse transcription PCR and in situ hybridization assay to detect the virus.

copyright Devonyu/Thinkstock
While Zika virus antigens have previously been detected in placentas and in fetal or neonatal brains, this does not necessarily indicate virus replication, the authors wrote (Emerg Infect Dis. 2016 Dec 14. doi: 10.3201/eid2303.161499).

“Nevertheless, localization of replicating Zika virus RNA directly in the tissues of patients with congenital and pregnancy-associated infections is critical for identifying cellular targets of Zika virus infection and virus persistence in various tissues and for further investigating the mechanism of Zika virus intrauterine transmission,” Dr. Bhatnagar said.

Using RT-PCR, the researchers were able to isolate Zika virus RNA from 32 (62%) of the case-patients – all 8 infants with microcephaly who died, and 24 women.

There were no major clinical differences between the women who tested positive for Zika virus with RT-PCR and those who tested negative; the most common symptoms in both groups were rash, fever, arthralgia, headache and conjunctivitis.

Among women who had an adverse pregnancy or birth outcome, 24 (75%) tested positive for Zika virus via RT-PCR, compared to 8 (36%) women with live-born healthy infants (P = .0082).

Symptom onset during the first trimester was associated with a significantly higher risk of adverse pregnancy and birth outcomes. Of the 24 women with positive RT-PCR results and adverse pregnancy outcomes, 23 had symptom onset during the first trimester, while all 8 patients with positive RT-PCR results but healthy infants had symptom onset in the third trimester (P less than .0001).

There were eight cases of infants with microcephaly who died within a few minutes to 2 months after birth, and five women who delivered live infants with microcephaly who survived.

All but one of these tested positive for Zika virus by RT-PCR, either in brain tissue or placental/fetal tissue, and all the women experienced symptom onset during the first trimester. Zika virus was not detected in other tissues from the infants.

Researchers also found that the levels of Zika virus RNA in the brain tissues of the infants who had microcephaly and died were around 1,200-fold higher than the levels observed in second or third trimester or full-term placentas.

Using in situ hybridization assays, researchers found Zika virus RNA in half of the tissues of the 32 case-patients who tested positive with RT-PCR.

“Zika virus replicative RNA, detected by using sense probe, was observed in the neural cells, neurons, and degenerating glial cells within the cerebral cortex of the brain,” the authors wrote.

Zika virus genomic and replicative RNA also was found in the placental chorionic villi – predominantly in the Hofbauer cells – in 9 (75%) of the 12 women with positive RT-PCR results who had experienced an adverse pregnancy outcome during the first or second trimester. The authors said this indicated the possibility that the Hofbauer cells may play a role in disseminating or transferring the virus to the fetal brain.

“This article highlights the value of tissue analysis to expand opportunities to diagnose Zika virus congenital and pregnancy-associated infections and to enhance the understanding of mechanism of Zika virus intrauterine transmission and pathogenesis,” the authors wrote. “In addition, the tissue-based RT-PCRs extend the time frame for Zika virus detection and particularly help to establish a diagnosis retrospectively, enabling pregnant women and their health care providers to identify the cause of severe microcephaly or fetal loss.”

No conflicts of interest were declared.

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FROM EMERGING INFECTIOUS DISEASES

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Key clinical point: Researchers isolated replicative Zika virus RNA from the brain tissue of infants with microcephaly, and the placental tissues of women suspected of being infected with Zika virus during pregnancy.

Major finding: Among women who had an adverse pregnancy or birth outcome, 75% tested positive for Zika virus via RT-PCR, compared to 36% of women with live-born healthy infants.

Data source: Case series of 8 infants with microcephaly who died and 44 women thought to have been infected with Zika virus during pregnancy.

Disclosures: No conflicts of interest were declared.

Big data ready to revolutionize infectious diseases research

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Fri, 01/18/2019 - 16:25

 

An all-encompassing definition of “big data” in health care remains elusive, but most researchers and public health experts believe big data may be poised to revolutionize the field of infectious diseases research.

Big data could provide the means to finally achieve effective and timely surveillance systems, which form a “pillar of infectious disease control,” according to Shweta Bansal, PhD, of the department of biology, Georgetown University, Washington, and her associates (J Infect Dis. 2016 Nov;214[S4]:S375-9. doi: 10.1093/infdis/jiw400).

copyright Sebastian Duda/Thinkstock
For infectious diseases researchers, surveillance systems are critical, as they track disease incidence and mortality rates as pathogens spread across the globe. “An ideal surveillance system is representative of the population, flexible, economic, and resilient, with timely reporting and validation of its outputs,” Lone Simonsen, PhD, of the department of public health, University of Copenhagen, Denmark, and her associates wrote in a supplemental article (J Infect Dis. 2016 Nov;214[S4]:S380-5. doi: 10.1093/infdis/jiw376).

“Further, full situational awareness requires availability of multiple surveillance data streams that capture mild and severe clinical outcomes (death certificates, hospital admissions, and emergency department and outpatient visits), as well as laboratory-based information (confirmed cases, genetic sequences, and serologic findings),” Dr. Simonsen added.

But unlike marketing or meteorology, two fields that have “perfected the art of real-time acquisition and analysis of highly resolved digital data,” the field of infectious diseases research has suffered from slow and incomplete surveillance of emerging and reemerging pathogens and pandemics, Dr. Bansal said.

What has changed in recent years is that physicians and researchers now have better access to patient information. Today, electronic health records and nontraditional patient data sources such as social media and remote sensing technology provide multiple surveillance data streams, and millions of people around the world can participate as the Internet, cell phones, and computers pervade even low income countries.

Several private and federal public health agencies have already launched successful initiatives “to use electronic data and patient records in a more timely fashion to track important events,” Dr. Simonsen said. For example, the Food and Drug Administration’s Sentinel Initiative aims to augment traditional surveillance (which relies on passive case reporting by physicians) with private sector electronic health data to identify severe adverse drug events.

The Centers for Disease Control and Prevention’s BioSense platform collects electronic health records to achieve “real-time awareness and tracking of pandemic influenza or any other novel health threat.” Google tracks influenza epidemics by analyzing Internet search query data. In Germany, researchers use medical claims data to track vaccination rates. In Canada, public health analysts compile multiple sources of disease outbreak information into online computational systems and then use this information to identify and track novel outbreaks and drug resistance.

The authors of these two papers warn that while big data is promising, it must be “balanced by caution.” Privacy concerns, barriers in access to e-health systems, and ill-fitting big data models must be addressed, and continued validation against traditional surveillance systems is imperative.

The authors of both papers reported no relevant conflicts of interest.

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An all-encompassing definition of “big data” in health care remains elusive, but most researchers and public health experts believe big data may be poised to revolutionize the field of infectious diseases research.

Big data could provide the means to finally achieve effective and timely surveillance systems, which form a “pillar of infectious disease control,” according to Shweta Bansal, PhD, of the department of biology, Georgetown University, Washington, and her associates (J Infect Dis. 2016 Nov;214[S4]:S375-9. doi: 10.1093/infdis/jiw400).

copyright Sebastian Duda/Thinkstock
For infectious diseases researchers, surveillance systems are critical, as they track disease incidence and mortality rates as pathogens spread across the globe. “An ideal surveillance system is representative of the population, flexible, economic, and resilient, with timely reporting and validation of its outputs,” Lone Simonsen, PhD, of the department of public health, University of Copenhagen, Denmark, and her associates wrote in a supplemental article (J Infect Dis. 2016 Nov;214[S4]:S380-5. doi: 10.1093/infdis/jiw376).

“Further, full situational awareness requires availability of multiple surveillance data streams that capture mild and severe clinical outcomes (death certificates, hospital admissions, and emergency department and outpatient visits), as well as laboratory-based information (confirmed cases, genetic sequences, and serologic findings),” Dr. Simonsen added.

But unlike marketing or meteorology, two fields that have “perfected the art of real-time acquisition and analysis of highly resolved digital data,” the field of infectious diseases research has suffered from slow and incomplete surveillance of emerging and reemerging pathogens and pandemics, Dr. Bansal said.

What has changed in recent years is that physicians and researchers now have better access to patient information. Today, electronic health records and nontraditional patient data sources such as social media and remote sensing technology provide multiple surveillance data streams, and millions of people around the world can participate as the Internet, cell phones, and computers pervade even low income countries.

Several private and federal public health agencies have already launched successful initiatives “to use electronic data and patient records in a more timely fashion to track important events,” Dr. Simonsen said. For example, the Food and Drug Administration’s Sentinel Initiative aims to augment traditional surveillance (which relies on passive case reporting by physicians) with private sector electronic health data to identify severe adverse drug events.

The Centers for Disease Control and Prevention’s BioSense platform collects electronic health records to achieve “real-time awareness and tracking of pandemic influenza or any other novel health threat.” Google tracks influenza epidemics by analyzing Internet search query data. In Germany, researchers use medical claims data to track vaccination rates. In Canada, public health analysts compile multiple sources of disease outbreak information into online computational systems and then use this information to identify and track novel outbreaks and drug resistance.

The authors of these two papers warn that while big data is promising, it must be “balanced by caution.” Privacy concerns, barriers in access to e-health systems, and ill-fitting big data models must be addressed, and continued validation against traditional surveillance systems is imperative.

The authors of both papers reported no relevant conflicts of interest.

 

An all-encompassing definition of “big data” in health care remains elusive, but most researchers and public health experts believe big data may be poised to revolutionize the field of infectious diseases research.

Big data could provide the means to finally achieve effective and timely surveillance systems, which form a “pillar of infectious disease control,” according to Shweta Bansal, PhD, of the department of biology, Georgetown University, Washington, and her associates (J Infect Dis. 2016 Nov;214[S4]:S375-9. doi: 10.1093/infdis/jiw400).

copyright Sebastian Duda/Thinkstock
For infectious diseases researchers, surveillance systems are critical, as they track disease incidence and mortality rates as pathogens spread across the globe. “An ideal surveillance system is representative of the population, flexible, economic, and resilient, with timely reporting and validation of its outputs,” Lone Simonsen, PhD, of the department of public health, University of Copenhagen, Denmark, and her associates wrote in a supplemental article (J Infect Dis. 2016 Nov;214[S4]:S380-5. doi: 10.1093/infdis/jiw376).

“Further, full situational awareness requires availability of multiple surveillance data streams that capture mild and severe clinical outcomes (death certificates, hospital admissions, and emergency department and outpatient visits), as well as laboratory-based information (confirmed cases, genetic sequences, and serologic findings),” Dr. Simonsen added.

But unlike marketing or meteorology, two fields that have “perfected the art of real-time acquisition and analysis of highly resolved digital data,” the field of infectious diseases research has suffered from slow and incomplete surveillance of emerging and reemerging pathogens and pandemics, Dr. Bansal said.

What has changed in recent years is that physicians and researchers now have better access to patient information. Today, electronic health records and nontraditional patient data sources such as social media and remote sensing technology provide multiple surveillance data streams, and millions of people around the world can participate as the Internet, cell phones, and computers pervade even low income countries.

Several private and federal public health agencies have already launched successful initiatives “to use electronic data and patient records in a more timely fashion to track important events,” Dr. Simonsen said. For example, the Food and Drug Administration’s Sentinel Initiative aims to augment traditional surveillance (which relies on passive case reporting by physicians) with private sector electronic health data to identify severe adverse drug events.

The Centers for Disease Control and Prevention’s BioSense platform collects electronic health records to achieve “real-time awareness and tracking of pandemic influenza or any other novel health threat.” Google tracks influenza epidemics by analyzing Internet search query data. In Germany, researchers use medical claims data to track vaccination rates. In Canada, public health analysts compile multiple sources of disease outbreak information into online computational systems and then use this information to identify and track novel outbreaks and drug resistance.

The authors of these two papers warn that while big data is promising, it must be “balanced by caution.” Privacy concerns, barriers in access to e-health systems, and ill-fitting big data models must be addressed, and continued validation against traditional surveillance systems is imperative.

The authors of both papers reported no relevant conflicts of interest.

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FROM THE JOURNAL OF INFECTIOUS DISEASES

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Combine qSOFA and SIRS for best sepsis score

Screen with SIRS, admit with qSOFA
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– Instead of replacing the Systemic Inflammatory Response Syndrome (SIRS) score with the new quick Sequential Organ Failure Assessment (qSOFA) score to identify severe sepsis patients, it might be best to use both, according to two studies presented at the American College of Chest Physicians annual meeting.

 

The gold standard 3rd International Consensus Definitions for Sepsis and Septic Shock Task Force recently introduced qSOFA to replace SIRS, in part because SIRS is too sensitive. With criteria that include a temperature above 38° C; a heart rate above 90 bpm, and a respiratory rate above 20 breaths per minute, it’s possible to score positive on SIRS by walking up a flight of stairs, audience members at the study presentations noted.

The first study at the meeting session – a prospective cohort of 152 patients scored by both systems within 8 hours of ICU admission at the New York–Presbyterian Hospital – found that qSOFA was slightly better at predicting in-hospital mortality and ICU-free days, but no better than SIRS at predicting ventilator- or organ failure–free days.

However, of the 36% of patients (55) who met only one of the three qSOFA criteria - a respiratory rate of 22 breaths per minute, altered mental status, or a systolic blood pressure of 100 mg Hg or less - 6% (3) died in the hospital. Of those patients, two-thirds (2) were SIRS positive, meaning that they met two or more SIRS criteria.

“Having a borderline qSOFA of 1 point, which is considered negative, with the addition of having SIRS criteria, should raise concerns that patients need further evaluation. SIRS criteria should not be [entirely] discarded” in favor of qSOFA, said lead investigator Eli Finkelsztein, MD, of the New York–Presbyterian Hospital in New York City

The second study – a review of 6,811 severe sepsis/septic shock patients scored by both systems within 3 hours of emergency department admission at the University of Kansas Hospital emergency department in Kansas City – found that the two scores performed largely the same when it came to predicting ICU admission and 30-day mortality, but that people who met two or more criteria in both systems were of special concern.

Twenty-five percent of patients (1,713) scored 2 or more on both SIRS and qSOFA. These patients were more likely to be admitted to the ICU and be readmitted to the hospital after a month, compared with those patients who were positive in only one scoring system or negative in both. Additional factors associated with these patients were that they had the longest ICU and hospital lengths of stay. Two hundred (12%) of these patients scoring 2 or more on both SIRS and qSOFA died within 30 days.

“SIRS criteria continue to be more sensitive at identifying severe sepsis, but they are equally as accurate [as qSOFA criteria] at predicting adverse patient outcomes,” said lead investigator and Kansas University medical student Amanda Deis.

SIRS and qSOFA take only a few seconds to assess at the bedside. Using both builds “a clinical picture,” she said.

There was no industry funding for the work, and the investigators had no relevant financial disclosures.
 

Body

Everybody got fed up with SIRS because it’s overly sensitive, but now we’ve swung in the other direction. It’s absolutely true that qSOFA is more specific, but one of the presenters had a 6% rate of qSOFA missing sick patients.

We want to be somewhere in the middle in terms of not missing too many of these cases. I thought 6% was reasonable, but others may not.

Dr. Zaza Cohen
Dr. Zaza Cohen
Maybe a combination of the two is best. Using SIRS as ICU screening criteria might be a good idea; the ICU physician could then come in and use qSOFA to determine if someone needs to be admitted to the ICU.

 

Zaza Cohen, MD, is the director of critical care at Mountainside Hospital in Montclair, N.J. He moderated - but was not involved with - the two studies.

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Body

Everybody got fed up with SIRS because it’s overly sensitive, but now we’ve swung in the other direction. It’s absolutely true that qSOFA is more specific, but one of the presenters had a 6% rate of qSOFA missing sick patients.

We want to be somewhere in the middle in terms of not missing too many of these cases. I thought 6% was reasonable, but others may not.

Dr. Zaza Cohen
Dr. Zaza Cohen
Maybe a combination of the two is best. Using SIRS as ICU screening criteria might be a good idea; the ICU physician could then come in and use qSOFA to determine if someone needs to be admitted to the ICU.

 

Zaza Cohen, MD, is the director of critical care at Mountainside Hospital in Montclair, N.J. He moderated - but was not involved with - the two studies.

Body

Everybody got fed up with SIRS because it’s overly sensitive, but now we’ve swung in the other direction. It’s absolutely true that qSOFA is more specific, but one of the presenters had a 6% rate of qSOFA missing sick patients.

We want to be somewhere in the middle in terms of not missing too many of these cases. I thought 6% was reasonable, but others may not.

Dr. Zaza Cohen
Dr. Zaza Cohen
Maybe a combination of the two is best. Using SIRS as ICU screening criteria might be a good idea; the ICU physician could then come in and use qSOFA to determine if someone needs to be admitted to the ICU.

 

Zaza Cohen, MD, is the director of critical care at Mountainside Hospital in Montclair, N.J. He moderated - but was not involved with - the two studies.

Title
Screen with SIRS, admit with qSOFA
Screen with SIRS, admit with qSOFA

– Instead of replacing the Systemic Inflammatory Response Syndrome (SIRS) score with the new quick Sequential Organ Failure Assessment (qSOFA) score to identify severe sepsis patients, it might be best to use both, according to two studies presented at the American College of Chest Physicians annual meeting.

 

The gold standard 3rd International Consensus Definitions for Sepsis and Septic Shock Task Force recently introduced qSOFA to replace SIRS, in part because SIRS is too sensitive. With criteria that include a temperature above 38° C; a heart rate above 90 bpm, and a respiratory rate above 20 breaths per minute, it’s possible to score positive on SIRS by walking up a flight of stairs, audience members at the study presentations noted.

The first study at the meeting session – a prospective cohort of 152 patients scored by both systems within 8 hours of ICU admission at the New York–Presbyterian Hospital – found that qSOFA was slightly better at predicting in-hospital mortality and ICU-free days, but no better than SIRS at predicting ventilator- or organ failure–free days.

However, of the 36% of patients (55) who met only one of the three qSOFA criteria - a respiratory rate of 22 breaths per minute, altered mental status, or a systolic blood pressure of 100 mg Hg or less - 6% (3) died in the hospital. Of those patients, two-thirds (2) were SIRS positive, meaning that they met two or more SIRS criteria.

“Having a borderline qSOFA of 1 point, which is considered negative, with the addition of having SIRS criteria, should raise concerns that patients need further evaluation. SIRS criteria should not be [entirely] discarded” in favor of qSOFA, said lead investigator Eli Finkelsztein, MD, of the New York–Presbyterian Hospital in New York City

The second study – a review of 6,811 severe sepsis/septic shock patients scored by both systems within 3 hours of emergency department admission at the University of Kansas Hospital emergency department in Kansas City – found that the two scores performed largely the same when it came to predicting ICU admission and 30-day mortality, but that people who met two or more criteria in both systems were of special concern.

Twenty-five percent of patients (1,713) scored 2 or more on both SIRS and qSOFA. These patients were more likely to be admitted to the ICU and be readmitted to the hospital after a month, compared with those patients who were positive in only one scoring system or negative in both. Additional factors associated with these patients were that they had the longest ICU and hospital lengths of stay. Two hundred (12%) of these patients scoring 2 or more on both SIRS and qSOFA died within 30 days.

“SIRS criteria continue to be more sensitive at identifying severe sepsis, but they are equally as accurate [as qSOFA criteria] at predicting adverse patient outcomes,” said lead investigator and Kansas University medical student Amanda Deis.

SIRS and qSOFA take only a few seconds to assess at the bedside. Using both builds “a clinical picture,” she said.

There was no industry funding for the work, and the investigators had no relevant financial disclosures.
 

– Instead of replacing the Systemic Inflammatory Response Syndrome (SIRS) score with the new quick Sequential Organ Failure Assessment (qSOFA) score to identify severe sepsis patients, it might be best to use both, according to two studies presented at the American College of Chest Physicians annual meeting.

 

The gold standard 3rd International Consensus Definitions for Sepsis and Septic Shock Task Force recently introduced qSOFA to replace SIRS, in part because SIRS is too sensitive. With criteria that include a temperature above 38° C; a heart rate above 90 bpm, and a respiratory rate above 20 breaths per minute, it’s possible to score positive on SIRS by walking up a flight of stairs, audience members at the study presentations noted.

The first study at the meeting session – a prospective cohort of 152 patients scored by both systems within 8 hours of ICU admission at the New York–Presbyterian Hospital – found that qSOFA was slightly better at predicting in-hospital mortality and ICU-free days, but no better than SIRS at predicting ventilator- or organ failure–free days.

However, of the 36% of patients (55) who met only one of the three qSOFA criteria - a respiratory rate of 22 breaths per minute, altered mental status, or a systolic blood pressure of 100 mg Hg or less - 6% (3) died in the hospital. Of those patients, two-thirds (2) were SIRS positive, meaning that they met two or more SIRS criteria.

“Having a borderline qSOFA of 1 point, which is considered negative, with the addition of having SIRS criteria, should raise concerns that patients need further evaluation. SIRS criteria should not be [entirely] discarded” in favor of qSOFA, said lead investigator Eli Finkelsztein, MD, of the New York–Presbyterian Hospital in New York City

The second study – a review of 6,811 severe sepsis/septic shock patients scored by both systems within 3 hours of emergency department admission at the University of Kansas Hospital emergency department in Kansas City – found that the two scores performed largely the same when it came to predicting ICU admission and 30-day mortality, but that people who met two or more criteria in both systems were of special concern.

Twenty-five percent of patients (1,713) scored 2 or more on both SIRS and qSOFA. These patients were more likely to be admitted to the ICU and be readmitted to the hospital after a month, compared with those patients who were positive in only one scoring system or negative in both. Additional factors associated with these patients were that they had the longest ICU and hospital lengths of stay. Two hundred (12%) of these patients scoring 2 or more on both SIRS and qSOFA died within 30 days.

“SIRS criteria continue to be more sensitive at identifying severe sepsis, but they are equally as accurate [as qSOFA criteria] at predicting adverse patient outcomes,” said lead investigator and Kansas University medical student Amanda Deis.

SIRS and qSOFA take only a few seconds to assess at the bedside. Using both builds “a clinical picture,” she said.

There was no industry funding for the work, and the investigators had no relevant financial disclosures.
 

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AT CHEST 2016

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Key clinical point: Instead of replacing the Systemic Inflammatory Response Syndrome (SIRS) score with the new quick Sequential Organ Failure Assessment (qSOFA) score to identify severe sepsis patients, it might be best to use both.

Major finding: Of the 36% of patients who met only one of the three qSOFA criteria, 6% died in the hospital. Of those patients, two-thirds were SIRS positive, meaning that they met two or more SIRS criteria.

Data source: Two studies of almost 7,000 septic patients.

Disclosures: There was no industry funding for the work, and the investigators had no relevant financial disclosures.

Bezlotoxumab reduces CDI recurrence across antibiotic subgroups

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– The monoclonal antibody bezlotoxumab significantly reduces the risk of Clostridium difficile infection (CDI) recurrence in adults receiving standard of care antibiotic treatment, regardless of whether that treatment is with metronidazole, vancomycin, or fidaxomicin, according to an analysis of data from the MODIFY I and II trials.

Dr. Erik R. Dubberke
Of the 1,554 subjects included in the analysis, 781 (50.2%) received a single infusion of bezlotoxumab in addition to standard of care antibiotic therapy, and 773 (49.7%) received placebo. Overall, 48.5% received oral metronidazole and 48.5% received oral vancomycin either alone or with IV metronidazole as their standard of care antibiotic, and 3.6% received oral fidaxomicin alone or with IV metronidazole. Those being treated for recurrent CDI more often received vancomycin (71%), while those with primary CDI more often received metronidazole (60%), Dr. Dubberke said at the combined annual meetings of the Infectious Diseases Society of America, the Society of Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Consistent with the overall study results, clinical cure rates were similar with bezlotoxumab and placebo, regardless of the standard of care antibiotic received (80% vs. 80.3%, respectively, overall; 81% vs. 81.3% in the metronidazole group; 78.5% vs. 79.6% in the vancomycin group; and 86.7% vs. 76.9% in the fidaxomicin group), he said.

However, CDI recurrence rates were lower among those who received bezlotoxumab, compared with those who received placebo in all three standard of care subgroups, with 10%, 15%, and 12% fewer bezlotoxumab vs. placebo patients experiencing recurrence in the metronidazole, vancomycin, and fidaxomicin groups, respectively, and 12% fewer experiencing recurrence overall.

The primary endpoint of CDI recurrence was defined in the studies as a new episode of diarrhea (at least three unformed stools in 24 hours) and a positive stool test for toxigenic C. difficile after clinical cure of the baseline CDI episode. Clinical cure was defined as standard of care antibiotics given for 14 days or less and no diarrhea for 2 consecutive days after completing standard of care treatment.

Of note, the patients in the vancomycin group were older and sicker, and had more risk factors for CDI, he said, noting, for example, that 57% of vancomycin patients were aged at least 65 years and 33% were aged at least 75 years, vs. 46% and 26% for metronidazole, respectively, and 46% and 18% for fidaxomicin; 72% of vancomycin patients were inpatients, compared with 65% and 50% of metronidazole and fidaxomicin patients.

Further, 19% of vancomycin patients, vs. 13% and 14% of metronidazole and fidaxomicin patients met criteria for severe CDI.

The findings of the current analysis are important, because the incidence of CDI recurrence is about 25%, and the risk increases with each subsequent recurrence, Dr. Dubberke said, concluding that this novel, nonantibiotic approach to prevention of CDI recurrence using bezlotoxumab, which recently received Food and Drug Administration approval for this indication, is of benefit for reducing that risk, regardless of the antibiotic used as part of standard of care therapy for CDI.

Dr. Dubberke reported serving as an investigator, adviser and/or consultant for Merck, Rebiotix, Sanofi Pasteur, and Summit, and receiving consultant fees and/or grant/research support from these companies.

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– The monoclonal antibody bezlotoxumab significantly reduces the risk of Clostridium difficile infection (CDI) recurrence in adults receiving standard of care antibiotic treatment, regardless of whether that treatment is with metronidazole, vancomycin, or fidaxomicin, according to an analysis of data from the MODIFY I and II trials.

Dr. Erik R. Dubberke
Of the 1,554 subjects included in the analysis, 781 (50.2%) received a single infusion of bezlotoxumab in addition to standard of care antibiotic therapy, and 773 (49.7%) received placebo. Overall, 48.5% received oral metronidazole and 48.5% received oral vancomycin either alone or with IV metronidazole as their standard of care antibiotic, and 3.6% received oral fidaxomicin alone or with IV metronidazole. Those being treated for recurrent CDI more often received vancomycin (71%), while those with primary CDI more often received metronidazole (60%), Dr. Dubberke said at the combined annual meetings of the Infectious Diseases Society of America, the Society of Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Consistent with the overall study results, clinical cure rates were similar with bezlotoxumab and placebo, regardless of the standard of care antibiotic received (80% vs. 80.3%, respectively, overall; 81% vs. 81.3% in the metronidazole group; 78.5% vs. 79.6% in the vancomycin group; and 86.7% vs. 76.9% in the fidaxomicin group), he said.

However, CDI recurrence rates were lower among those who received bezlotoxumab, compared with those who received placebo in all three standard of care subgroups, with 10%, 15%, and 12% fewer bezlotoxumab vs. placebo patients experiencing recurrence in the metronidazole, vancomycin, and fidaxomicin groups, respectively, and 12% fewer experiencing recurrence overall.

The primary endpoint of CDI recurrence was defined in the studies as a new episode of diarrhea (at least three unformed stools in 24 hours) and a positive stool test for toxigenic C. difficile after clinical cure of the baseline CDI episode. Clinical cure was defined as standard of care antibiotics given for 14 days or less and no diarrhea for 2 consecutive days after completing standard of care treatment.

Of note, the patients in the vancomycin group were older and sicker, and had more risk factors for CDI, he said, noting, for example, that 57% of vancomycin patients were aged at least 65 years and 33% were aged at least 75 years, vs. 46% and 26% for metronidazole, respectively, and 46% and 18% for fidaxomicin; 72% of vancomycin patients were inpatients, compared with 65% and 50% of metronidazole and fidaxomicin patients.

Further, 19% of vancomycin patients, vs. 13% and 14% of metronidazole and fidaxomicin patients met criteria for severe CDI.

The findings of the current analysis are important, because the incidence of CDI recurrence is about 25%, and the risk increases with each subsequent recurrence, Dr. Dubberke said, concluding that this novel, nonantibiotic approach to prevention of CDI recurrence using bezlotoxumab, which recently received Food and Drug Administration approval for this indication, is of benefit for reducing that risk, regardless of the antibiotic used as part of standard of care therapy for CDI.

Dr. Dubberke reported serving as an investigator, adviser and/or consultant for Merck, Rebiotix, Sanofi Pasteur, and Summit, and receiving consultant fees and/or grant/research support from these companies.

– The monoclonal antibody bezlotoxumab significantly reduces the risk of Clostridium difficile infection (CDI) recurrence in adults receiving standard of care antibiotic treatment, regardless of whether that treatment is with metronidazole, vancomycin, or fidaxomicin, according to an analysis of data from the MODIFY I and II trials.

Dr. Erik R. Dubberke
Of the 1,554 subjects included in the analysis, 781 (50.2%) received a single infusion of bezlotoxumab in addition to standard of care antibiotic therapy, and 773 (49.7%) received placebo. Overall, 48.5% received oral metronidazole and 48.5% received oral vancomycin either alone or with IV metronidazole as their standard of care antibiotic, and 3.6% received oral fidaxomicin alone or with IV metronidazole. Those being treated for recurrent CDI more often received vancomycin (71%), while those with primary CDI more often received metronidazole (60%), Dr. Dubberke said at the combined annual meetings of the Infectious Diseases Society of America, the Society of Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Consistent with the overall study results, clinical cure rates were similar with bezlotoxumab and placebo, regardless of the standard of care antibiotic received (80% vs. 80.3%, respectively, overall; 81% vs. 81.3% in the metronidazole group; 78.5% vs. 79.6% in the vancomycin group; and 86.7% vs. 76.9% in the fidaxomicin group), he said.

However, CDI recurrence rates were lower among those who received bezlotoxumab, compared with those who received placebo in all three standard of care subgroups, with 10%, 15%, and 12% fewer bezlotoxumab vs. placebo patients experiencing recurrence in the metronidazole, vancomycin, and fidaxomicin groups, respectively, and 12% fewer experiencing recurrence overall.

The primary endpoint of CDI recurrence was defined in the studies as a new episode of diarrhea (at least three unformed stools in 24 hours) and a positive stool test for toxigenic C. difficile after clinical cure of the baseline CDI episode. Clinical cure was defined as standard of care antibiotics given for 14 days or less and no diarrhea for 2 consecutive days after completing standard of care treatment.

Of note, the patients in the vancomycin group were older and sicker, and had more risk factors for CDI, he said, noting, for example, that 57% of vancomycin patients were aged at least 65 years and 33% were aged at least 75 years, vs. 46% and 26% for metronidazole, respectively, and 46% and 18% for fidaxomicin; 72% of vancomycin patients were inpatients, compared with 65% and 50% of metronidazole and fidaxomicin patients.

Further, 19% of vancomycin patients, vs. 13% and 14% of metronidazole and fidaxomicin patients met criteria for severe CDI.

The findings of the current analysis are important, because the incidence of CDI recurrence is about 25%, and the risk increases with each subsequent recurrence, Dr. Dubberke said, concluding that this novel, nonantibiotic approach to prevention of CDI recurrence using bezlotoxumab, which recently received Food and Drug Administration approval for this indication, is of benefit for reducing that risk, regardless of the antibiotic used as part of standard of care therapy for CDI.

Dr. Dubberke reported serving as an investigator, adviser and/or consultant for Merck, Rebiotix, Sanofi Pasteur, and Summit, and receiving consultant fees and/or grant/research support from these companies.

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Key clinical point: Bezlotoxumab significantly reduces CDI recurrence risk in adults receiving antibiotic treatment, regardless of standard of care antibiotic used.

Major finding: 12% fewer bezlotoxumab vs. placebo patients experienced CDI recurrence.

Data source: A prespecified analysis of data from 1,554 subjects from the MODIFY I and II trials.

Disclosures: Dr. Dubberke reported serving as an investigator, adviser, and/or consultant for Merck, Rebiotix, Sanofi Pasteur, and Summit, and receiving consultant fees and/or grant/research support from these companies.

Health care workers at risk for mild MERS-CoV infections

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Health care workers directly caring for patients with Middle East respiratory syndrome coronavirus (MERS-CoV) are more highly predisposed to contracting the virus, but in a milder form than that of their patients, thus making it difficult to diagnose and treat.

In a study published in Emerging Infectious Diseases, health care professionals (HCP) from the King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia, were examined to determine their likelihood for getting MERS-CoV based on their proximity to patients who already had it.

Courtesy CDC; Maureen Metcalfe and Azaibi Tamin


“Healthcare settings are important amplifiers of transmission,” explained the investigators, led by Basem M. Alraddadi, MD. “Current MERS-CoV infection control recommendations are based on experience with other viruses rather than on a complete understanding of the epidemiology of MERS-CoV transmission.”

Dr. Alraddadi and his coinvestigators identified 363 HCP, all of whom would be placed into one of three cohorts based on the department in which they worked most extensively: the Medical Intensive Care Unit (MICU), the emergency department (ED), and the neurology unit. A total of 292 HCP were ultimately enrolled in the study: 131 in MICU, 127 in ED, and 34 in neurology. After 9 subjects were excluded because of unavailability of serum specimens, 128 MICU, 122 ED, and 33 neurology unit workers remained.

While none of the neurology unit workers contracted the virus, 15 MICU workers (11.7%) and 5 ED workers (4.1%) did, for a total of 20 out of the 250 subjects in those two cohorts (8%). Radiology technicians were the most susceptible, as 5 of 17 (29.4%) got the virus, followed by 13 of 138 nurses (9.4%), 1 of 31 respiratory therapists (3.2%), and 1 of 41 physicians (2.4%).

“HCP who reported always covering their nose and mouth with either a medical mask or N95 respirator had lower risk for infection than did HCP reporting not always or never doing so, [while] those who reported always using N95 respirators for direct patient contact were less likely to be seropositive, a trend that approached statistical significance (P = .07),” the authors noted.

The most frequent symptoms reported by those surveyed were muscle pain, fevers, headaches, dry cough, and shortness of breath. In the 20-case HCP sample, however, 12 subjects (60%) only had mild illness while 3 (15%) were asymptomatic, making it very hard to diagnose and treat their infection. Three subjects (15%) had severe illness, while another two (10%) had moderate illness, meaning they were admitted to hospital but did not require any mechanical ventilation.

“Our study did not identify strong associations with underlying chronic illnesses, most likely because the prevalence of such conditions was low ([less than] 10%) in this population, [but] HCPs with a history of smoking had a risk for infection almost 3 times that of nonsmokers,” the authors wrote (Emerg Infect Dis. 2016 Nov. doi: 10.3201/eid2211.160920).

The Ministry of Health of Saudi Arabia and the Centers for Disease Control and Prevention funded the study. Dr. Alraddadi and his coauthors did not report any disclosures.
 

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Health care workers directly caring for patients with Middle East respiratory syndrome coronavirus (MERS-CoV) are more highly predisposed to contracting the virus, but in a milder form than that of their patients, thus making it difficult to diagnose and treat.

In a study published in Emerging Infectious Diseases, health care professionals (HCP) from the King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia, were examined to determine their likelihood for getting MERS-CoV based on their proximity to patients who already had it.

Courtesy CDC; Maureen Metcalfe and Azaibi Tamin


“Healthcare settings are important amplifiers of transmission,” explained the investigators, led by Basem M. Alraddadi, MD. “Current MERS-CoV infection control recommendations are based on experience with other viruses rather than on a complete understanding of the epidemiology of MERS-CoV transmission.”

Dr. Alraddadi and his coinvestigators identified 363 HCP, all of whom would be placed into one of three cohorts based on the department in which they worked most extensively: the Medical Intensive Care Unit (MICU), the emergency department (ED), and the neurology unit. A total of 292 HCP were ultimately enrolled in the study: 131 in MICU, 127 in ED, and 34 in neurology. After 9 subjects were excluded because of unavailability of serum specimens, 128 MICU, 122 ED, and 33 neurology unit workers remained.

While none of the neurology unit workers contracted the virus, 15 MICU workers (11.7%) and 5 ED workers (4.1%) did, for a total of 20 out of the 250 subjects in those two cohorts (8%). Radiology technicians were the most susceptible, as 5 of 17 (29.4%) got the virus, followed by 13 of 138 nurses (9.4%), 1 of 31 respiratory therapists (3.2%), and 1 of 41 physicians (2.4%).

“HCP who reported always covering their nose and mouth with either a medical mask or N95 respirator had lower risk for infection than did HCP reporting not always or never doing so, [while] those who reported always using N95 respirators for direct patient contact were less likely to be seropositive, a trend that approached statistical significance (P = .07),” the authors noted.

The most frequent symptoms reported by those surveyed were muscle pain, fevers, headaches, dry cough, and shortness of breath. In the 20-case HCP sample, however, 12 subjects (60%) only had mild illness while 3 (15%) were asymptomatic, making it very hard to diagnose and treat their infection. Three subjects (15%) had severe illness, while another two (10%) had moderate illness, meaning they were admitted to hospital but did not require any mechanical ventilation.

“Our study did not identify strong associations with underlying chronic illnesses, most likely because the prevalence of such conditions was low ([less than] 10%) in this population, [but] HCPs with a history of smoking had a risk for infection almost 3 times that of nonsmokers,” the authors wrote (Emerg Infect Dis. 2016 Nov. doi: 10.3201/eid2211.160920).

The Ministry of Health of Saudi Arabia and the Centers for Disease Control and Prevention funded the study. Dr. Alraddadi and his coauthors did not report any disclosures.
 

 

Health care workers directly caring for patients with Middle East respiratory syndrome coronavirus (MERS-CoV) are more highly predisposed to contracting the virus, but in a milder form than that of their patients, thus making it difficult to diagnose and treat.

In a study published in Emerging Infectious Diseases, health care professionals (HCP) from the King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia, were examined to determine their likelihood for getting MERS-CoV based on their proximity to patients who already had it.

Courtesy CDC; Maureen Metcalfe and Azaibi Tamin


“Healthcare settings are important amplifiers of transmission,” explained the investigators, led by Basem M. Alraddadi, MD. “Current MERS-CoV infection control recommendations are based on experience with other viruses rather than on a complete understanding of the epidemiology of MERS-CoV transmission.”

Dr. Alraddadi and his coinvestigators identified 363 HCP, all of whom would be placed into one of three cohorts based on the department in which they worked most extensively: the Medical Intensive Care Unit (MICU), the emergency department (ED), and the neurology unit. A total of 292 HCP were ultimately enrolled in the study: 131 in MICU, 127 in ED, and 34 in neurology. After 9 subjects were excluded because of unavailability of serum specimens, 128 MICU, 122 ED, and 33 neurology unit workers remained.

While none of the neurology unit workers contracted the virus, 15 MICU workers (11.7%) and 5 ED workers (4.1%) did, for a total of 20 out of the 250 subjects in those two cohorts (8%). Radiology technicians were the most susceptible, as 5 of 17 (29.4%) got the virus, followed by 13 of 138 nurses (9.4%), 1 of 31 respiratory therapists (3.2%), and 1 of 41 physicians (2.4%).

“HCP who reported always covering their nose and mouth with either a medical mask or N95 respirator had lower risk for infection than did HCP reporting not always or never doing so, [while] those who reported always using N95 respirators for direct patient contact were less likely to be seropositive, a trend that approached statistical significance (P = .07),” the authors noted.

The most frequent symptoms reported by those surveyed were muscle pain, fevers, headaches, dry cough, and shortness of breath. In the 20-case HCP sample, however, 12 subjects (60%) only had mild illness while 3 (15%) were asymptomatic, making it very hard to diagnose and treat their infection. Three subjects (15%) had severe illness, while another two (10%) had moderate illness, meaning they were admitted to hospital but did not require any mechanical ventilation.

“Our study did not identify strong associations with underlying chronic illnesses, most likely because the prevalence of such conditions was low ([less than] 10%) in this population, [but] HCPs with a history of smoking had a risk for infection almost 3 times that of nonsmokers,” the authors wrote (Emerg Infect Dis. 2016 Nov. doi: 10.3201/eid2211.160920).

The Ministry of Health of Saudi Arabia and the Centers for Disease Control and Prevention funded the study. Dr. Alraddadi and his coauthors did not report any disclosures.
 

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Key clinical point: Health care workers tending to patients with Middle East respiratory syndrome coronavirus are more likely to contract the virus, albeit in a milder form.

Major finding: Among workers who actually treated MERS-CoV patients, 20 out of 250 (8%) contracted the virus, while none of the clerical staff or patient transporters did.

Data source: Retrospective, single-center study of 363 health care personnel during May-June 2014.

Disclosures: The Ministry of Health of Saudi Arabia and the Centers for Disease Control and Prevention funded the study. The authors reported no financial disclosures.

ZMapp shows promise for Ebola treatment, but misses efficacy goal

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ZMapp, a potential monoclonal antibody treatment for Ebola virus disease, did not meet its efficacy goal in a clinical trial of patients in Liberia, Sierra Leone, and Guinea, according to a report in the New England Journal of Medicine.

ZMapp, developed by Mapp Biopharmaceutical, comprises three different laboratory-generated monoclonal antibodies. The drug targets the main surface protein of the Ebola virus. Earlier studies in nonhuman primates demonstrated that ZMapp had strong antiviral activity and prevented death when administered as late as 5 days after experimental infection with the Zaire Ebola virus strain.

©NIAID/Creative Commons License
Stringlike Ebola virus particles are shedding from an infected cell in this electron micrograph.
In the randomized, controlled trial known as PREVAIL II, 71 patients were evaluated, 36 of whom received ZMapp. In the ZMapp group, 8 out of 36 patients (22%) died from Ebola virus disease within 28 days of enrollment, compared with 13 of 35 patients (37%) who did not receive ZMapp. The probability that ZMapp plus the current standard of care was superior to the current standard of care was 91.2%, short of the study goal of 97.5%.

The process of ZMapp infusion was generally safe, with only one serious adverse event – hypertension – attributed to the infusion itself. Of the 93 infusions attempted in the ZMapp group, 8 were stopped because of adverse events, and 9 were slowed down to accommodate for side effects.

While ZMapp did not meet its goal, the relative risk of death was 40% lower in the ZMapp group then in the control group. Treatment with ZMapp was delayed for a week after patients became symptomatic, exceeding the 5-day window where ZMapp has been shown to have at least 90% effectiveness. In addition, of the eight patients who died in the ZMapp group, seven died before the second of the three planned ZMapp infusions were delivered.

The abrupt end to the Ebola epidemic prevented the ZMapp trial from being adequately completed. A goal of 100 patients in both groups was desired but could not be reached.

“Despite the concerted efforts of many dedicated researchers domestically and internationally who participated in this and other trials, the outbreak appears to have ended with no incontrovertible evidence that any single treatment intervention, or combination of interventions, was unequivocally superior to the types of supportive medical care typically provided,” the investigators said.

Find the full study in the New England Journal of Medicine (doi: 10.1056/NEJMoa1604330).
 

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ZMapp, a potential monoclonal antibody treatment for Ebola virus disease, did not meet its efficacy goal in a clinical trial of patients in Liberia, Sierra Leone, and Guinea, according to a report in the New England Journal of Medicine.

ZMapp, developed by Mapp Biopharmaceutical, comprises three different laboratory-generated monoclonal antibodies. The drug targets the main surface protein of the Ebola virus. Earlier studies in nonhuman primates demonstrated that ZMapp had strong antiviral activity and prevented death when administered as late as 5 days after experimental infection with the Zaire Ebola virus strain.

©NIAID/Creative Commons License
Stringlike Ebola virus particles are shedding from an infected cell in this electron micrograph.
In the randomized, controlled trial known as PREVAIL II, 71 patients were evaluated, 36 of whom received ZMapp. In the ZMapp group, 8 out of 36 patients (22%) died from Ebola virus disease within 28 days of enrollment, compared with 13 of 35 patients (37%) who did not receive ZMapp. The probability that ZMapp plus the current standard of care was superior to the current standard of care was 91.2%, short of the study goal of 97.5%.

The process of ZMapp infusion was generally safe, with only one serious adverse event – hypertension – attributed to the infusion itself. Of the 93 infusions attempted in the ZMapp group, 8 were stopped because of adverse events, and 9 were slowed down to accommodate for side effects.

While ZMapp did not meet its goal, the relative risk of death was 40% lower in the ZMapp group then in the control group. Treatment with ZMapp was delayed for a week after patients became symptomatic, exceeding the 5-day window where ZMapp has been shown to have at least 90% effectiveness. In addition, of the eight patients who died in the ZMapp group, seven died before the second of the three planned ZMapp infusions were delivered.

The abrupt end to the Ebola epidemic prevented the ZMapp trial from being adequately completed. A goal of 100 patients in both groups was desired but could not be reached.

“Despite the concerted efforts of many dedicated researchers domestically and internationally who participated in this and other trials, the outbreak appears to have ended with no incontrovertible evidence that any single treatment intervention, or combination of interventions, was unequivocally superior to the types of supportive medical care typically provided,” the investigators said.

Find the full study in the New England Journal of Medicine (doi: 10.1056/NEJMoa1604330).
 

 

ZMapp, a potential monoclonal antibody treatment for Ebola virus disease, did not meet its efficacy goal in a clinical trial of patients in Liberia, Sierra Leone, and Guinea, according to a report in the New England Journal of Medicine.

ZMapp, developed by Mapp Biopharmaceutical, comprises three different laboratory-generated monoclonal antibodies. The drug targets the main surface protein of the Ebola virus. Earlier studies in nonhuman primates demonstrated that ZMapp had strong antiviral activity and prevented death when administered as late as 5 days after experimental infection with the Zaire Ebola virus strain.

©NIAID/Creative Commons License
Stringlike Ebola virus particles are shedding from an infected cell in this electron micrograph.
In the randomized, controlled trial known as PREVAIL II, 71 patients were evaluated, 36 of whom received ZMapp. In the ZMapp group, 8 out of 36 patients (22%) died from Ebola virus disease within 28 days of enrollment, compared with 13 of 35 patients (37%) who did not receive ZMapp. The probability that ZMapp plus the current standard of care was superior to the current standard of care was 91.2%, short of the study goal of 97.5%.

The process of ZMapp infusion was generally safe, with only one serious adverse event – hypertension – attributed to the infusion itself. Of the 93 infusions attempted in the ZMapp group, 8 were stopped because of adverse events, and 9 were slowed down to accommodate for side effects.

While ZMapp did not meet its goal, the relative risk of death was 40% lower in the ZMapp group then in the control group. Treatment with ZMapp was delayed for a week after patients became symptomatic, exceeding the 5-day window where ZMapp has been shown to have at least 90% effectiveness. In addition, of the eight patients who died in the ZMapp group, seven died before the second of the three planned ZMapp infusions were delivered.

The abrupt end to the Ebola epidemic prevented the ZMapp trial from being adequately completed. A goal of 100 patients in both groups was desired but could not be reached.

“Despite the concerted efforts of many dedicated researchers domestically and internationally who participated in this and other trials, the outbreak appears to have ended with no incontrovertible evidence that any single treatment intervention, or combination of interventions, was unequivocally superior to the types of supportive medical care typically provided,” the investigators said.

Find the full study in the New England Journal of Medicine (doi: 10.1056/NEJMoa1604330).
 

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Further evidence links Zika, Guillain-Barré syndrome

Study is promising, but more work needs to be done
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Evidence of Zika virus found in Colombian patients with Guillain-Barré syndrome supports the theory that Zika virus infection and Guillain-Barré syndrome are related and could occur parainfectiously, according to a study published in the New England Journal of Medicine.

“Our study provides virologic evidence of [Zika virus] infection in patients with Guillain-Barré syndrome,” wrote Beatriz Parra, PhD, of the Hospital Universitario del Valle in Valle del Cauca, Colombia, and her coauthors (N Engl J Med. 2016 Oct 5. doi: 10.1056/NEJMoa1605564).

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The study looked at 68 patients with Guillain-Barré syndrome, all of whom received their diagnoses at one of six university-based health care centers across Colombia between January and March 2016. Median age was 47 years, 56% were male and 90% of mixed race. All 68 patients were evaluated clinically for Guillain-Barré syndrome and underwent neurologic evaluation as well. Of the 68 subjects, 42 also underwent laboratory testing to find Zika virus RNA in either blood, cerebrospinal fluid, or urine, via reverse-transcriptase polymerase chain reaction (RT-PCR) testing.

Results indicated that 66 (97%) of subjects had symptoms consistent with a Zika virus infection prior to the onset of Guillain-Barré syndrome. The median number of days between onset of Zika-like symptoms and the onset of Guillain-Barré syndrome was found to be 7 days (interquartile range, 3-10 days). Seventeen (40%) of the 42 patients who underwent laboratory testing tested positive for Zika virus RNA in their sample, with 16 of those 17 positive tests coming from urine samples. Additionally, 18 of the 42 laboratory-tested subjects had “clinical and immunologic findings [that] supported” a Zika virus infection.

“The onset of the Guillain-Barré syndrome can parallel the onset of systemic manifestations of [Zika virus] infection, indicating a so-called parainfectious onset, which suggests that factors different from the known postinfectious mechanisms may be present in [Zika virus]–related Guillain-Barré syndrome,” the authors explained, adding that 20 (48%) of the 42 laboratory-tested subjects had a parainfectious onset.

“RT-PCR testing of urine is a valuable diagnostic tool for the identification of [Zika virus] infection in patients with Guillain-Barré syndrome,” Dr. Parra and her coauthors concluded.

The study was funded by the Bart McLean Fund for Neuroimmunology Research, Johns Hopkins Project Restore, and the Universidad del Valle. Dr. Parra reported no relevant financial disclosures.

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Dr. Parra and her colleagues report in the Journal the results of a prospective study of 68 Colombian patients who had a syndrome consistent with the Guillain-Barré syndrome, 66 of whom had previously had symptoms of Zika virus (ZIKV) infection. Major strengths of this study include the documentation of a temporal relationship between the Guillain-Barré syndrome and ZIKV infection (marked by a substantial increase in the incidence of the Guillain-Barré syndrome after the introduction of ZIKV, from 20 to 90 cases per month throughout Colombia), the criteria applied for the diagnosis of the Guillain-Barré syndrome, and the molecular and serologic flavivirus data from analyses of serum, cerebrospinal fluid, and urine.

The difficulties in diagnosing ZIKV infection are borne out in this study, as only 17 patients had definitive laboratory evidence of recent ZIKV infection. Of these 17 patients, only 14 had electrophysiologic data consistent with the Guillain-Barré syndrome and therefore could have met Brighton level 1 diagnostic criteria for the syndrome. Among the 25 ZIKV PCR–negative patients, dengue virus (DENV) IgG antibodies were present in the cerebrospinal fluid of 12 patients and in the serum of 10 patients, and serum DENV IgM test results were positive in 1. These data raise the possibility of primary DENV infection and false-positive ZIKV serologic test results from cross reactivity.

Overall, the study by Dr. Parra and her colleagues supports the association between ZIKV and the Guillain-Barré syndrome, although confirmation in another cohort would strengthen this assertion. Although high rates of seropositivity may prove protective against further waves of ZIKV-related Guillain-Barré syndrome in Central and South America, the ZIKV pandemic is just beginning in North America and Africa, and an increase in the incidence of the Guillain-Barré syndrome may follow.
 

Jennifer A. Frontera, MD, is with the Cerebrovascular Center at the Cleveland Clinic in Cleveland. Ivan R.F. da Silva. MD, is with the Federal Fluminense University in Niterói, Brazil. These comments were adapted from their editorial accompanying the study ( N Engl J Med. 2016 Oct 5. doi: 10.1056/NEJMe1611840 ).

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Dr. Parra and her colleagues report in the Journal the results of a prospective study of 68 Colombian patients who had a syndrome consistent with the Guillain-Barré syndrome, 66 of whom had previously had symptoms of Zika virus (ZIKV) infection. Major strengths of this study include the documentation of a temporal relationship between the Guillain-Barré syndrome and ZIKV infection (marked by a substantial increase in the incidence of the Guillain-Barré syndrome after the introduction of ZIKV, from 20 to 90 cases per month throughout Colombia), the criteria applied for the diagnosis of the Guillain-Barré syndrome, and the molecular and serologic flavivirus data from analyses of serum, cerebrospinal fluid, and urine.

The difficulties in diagnosing ZIKV infection are borne out in this study, as only 17 patients had definitive laboratory evidence of recent ZIKV infection. Of these 17 patients, only 14 had electrophysiologic data consistent with the Guillain-Barré syndrome and therefore could have met Brighton level 1 diagnostic criteria for the syndrome. Among the 25 ZIKV PCR–negative patients, dengue virus (DENV) IgG antibodies were present in the cerebrospinal fluid of 12 patients and in the serum of 10 patients, and serum DENV IgM test results were positive in 1. These data raise the possibility of primary DENV infection and false-positive ZIKV serologic test results from cross reactivity.

Overall, the study by Dr. Parra and her colleagues supports the association between ZIKV and the Guillain-Barré syndrome, although confirmation in another cohort would strengthen this assertion. Although high rates of seropositivity may prove protective against further waves of ZIKV-related Guillain-Barré syndrome in Central and South America, the ZIKV pandemic is just beginning in North America and Africa, and an increase in the incidence of the Guillain-Barré syndrome may follow.
 

Jennifer A. Frontera, MD, is with the Cerebrovascular Center at the Cleveland Clinic in Cleveland. Ivan R.F. da Silva. MD, is with the Federal Fluminense University in Niterói, Brazil. These comments were adapted from their editorial accompanying the study ( N Engl J Med. 2016 Oct 5. doi: 10.1056/NEJMe1611840 ).

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Dr. Parra and her colleagues report in the Journal the results of a prospective study of 68 Colombian patients who had a syndrome consistent with the Guillain-Barré syndrome, 66 of whom had previously had symptoms of Zika virus (ZIKV) infection. Major strengths of this study include the documentation of a temporal relationship between the Guillain-Barré syndrome and ZIKV infection (marked by a substantial increase in the incidence of the Guillain-Barré syndrome after the introduction of ZIKV, from 20 to 90 cases per month throughout Colombia), the criteria applied for the diagnosis of the Guillain-Barré syndrome, and the molecular and serologic flavivirus data from analyses of serum, cerebrospinal fluid, and urine.

The difficulties in diagnosing ZIKV infection are borne out in this study, as only 17 patients had definitive laboratory evidence of recent ZIKV infection. Of these 17 patients, only 14 had electrophysiologic data consistent with the Guillain-Barré syndrome and therefore could have met Brighton level 1 diagnostic criteria for the syndrome. Among the 25 ZIKV PCR–negative patients, dengue virus (DENV) IgG antibodies were present in the cerebrospinal fluid of 12 patients and in the serum of 10 patients, and serum DENV IgM test results were positive in 1. These data raise the possibility of primary DENV infection and false-positive ZIKV serologic test results from cross reactivity.

Overall, the study by Dr. Parra and her colleagues supports the association between ZIKV and the Guillain-Barré syndrome, although confirmation in another cohort would strengthen this assertion. Although high rates of seropositivity may prove protective against further waves of ZIKV-related Guillain-Barré syndrome in Central and South America, the ZIKV pandemic is just beginning in North America and Africa, and an increase in the incidence of the Guillain-Barré syndrome may follow.
 

Jennifer A. Frontera, MD, is with the Cerebrovascular Center at the Cleveland Clinic in Cleveland. Ivan R.F. da Silva. MD, is with the Federal Fluminense University in Niterói, Brazil. These comments were adapted from their editorial accompanying the study ( N Engl J Med. 2016 Oct 5. doi: 10.1056/NEJMe1611840 ).

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Study is promising, but more work needs to be done
Study is promising, but more work needs to be done

 

Evidence of Zika virus found in Colombian patients with Guillain-Barré syndrome supports the theory that Zika virus infection and Guillain-Barré syndrome are related and could occur parainfectiously, according to a study published in the New England Journal of Medicine.

“Our study provides virologic evidence of [Zika virus] infection in patients with Guillain-Barré syndrome,” wrote Beatriz Parra, PhD, of the Hospital Universitario del Valle in Valle del Cauca, Colombia, and her coauthors (N Engl J Med. 2016 Oct 5. doi: 10.1056/NEJMoa1605564).

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The study looked at 68 patients with Guillain-Barré syndrome, all of whom received their diagnoses at one of six university-based health care centers across Colombia between January and March 2016. Median age was 47 years, 56% were male and 90% of mixed race. All 68 patients were evaluated clinically for Guillain-Barré syndrome and underwent neurologic evaluation as well. Of the 68 subjects, 42 also underwent laboratory testing to find Zika virus RNA in either blood, cerebrospinal fluid, or urine, via reverse-transcriptase polymerase chain reaction (RT-PCR) testing.

Results indicated that 66 (97%) of subjects had symptoms consistent with a Zika virus infection prior to the onset of Guillain-Barré syndrome. The median number of days between onset of Zika-like symptoms and the onset of Guillain-Barré syndrome was found to be 7 days (interquartile range, 3-10 days). Seventeen (40%) of the 42 patients who underwent laboratory testing tested positive for Zika virus RNA in their sample, with 16 of those 17 positive tests coming from urine samples. Additionally, 18 of the 42 laboratory-tested subjects had “clinical and immunologic findings [that] supported” a Zika virus infection.

“The onset of the Guillain-Barré syndrome can parallel the onset of systemic manifestations of [Zika virus] infection, indicating a so-called parainfectious onset, which suggests that factors different from the known postinfectious mechanisms may be present in [Zika virus]–related Guillain-Barré syndrome,” the authors explained, adding that 20 (48%) of the 42 laboratory-tested subjects had a parainfectious onset.

“RT-PCR testing of urine is a valuable diagnostic tool for the identification of [Zika virus] infection in patients with Guillain-Barré syndrome,” Dr. Parra and her coauthors concluded.

The study was funded by the Bart McLean Fund for Neuroimmunology Research, Johns Hopkins Project Restore, and the Universidad del Valle. Dr. Parra reported no relevant financial disclosures.

 

Evidence of Zika virus found in Colombian patients with Guillain-Barré syndrome supports the theory that Zika virus infection and Guillain-Barré syndrome are related and could occur parainfectiously, according to a study published in the New England Journal of Medicine.

“Our study provides virologic evidence of [Zika virus] infection in patients with Guillain-Barré syndrome,” wrote Beatriz Parra, PhD, of the Hospital Universitario del Valle in Valle del Cauca, Colombia, and her coauthors (N Engl J Med. 2016 Oct 5. doi: 10.1056/NEJMoa1605564).

Devonyu/Thinkstock
The study looked at 68 patients with Guillain-Barré syndrome, all of whom received their diagnoses at one of six university-based health care centers across Colombia between January and March 2016. Median age was 47 years, 56% were male and 90% of mixed race. All 68 patients were evaluated clinically for Guillain-Barré syndrome and underwent neurologic evaluation as well. Of the 68 subjects, 42 also underwent laboratory testing to find Zika virus RNA in either blood, cerebrospinal fluid, or urine, via reverse-transcriptase polymerase chain reaction (RT-PCR) testing.

Results indicated that 66 (97%) of subjects had symptoms consistent with a Zika virus infection prior to the onset of Guillain-Barré syndrome. The median number of days between onset of Zika-like symptoms and the onset of Guillain-Barré syndrome was found to be 7 days (interquartile range, 3-10 days). Seventeen (40%) of the 42 patients who underwent laboratory testing tested positive for Zika virus RNA in their sample, with 16 of those 17 positive tests coming from urine samples. Additionally, 18 of the 42 laboratory-tested subjects had “clinical and immunologic findings [that] supported” a Zika virus infection.

“The onset of the Guillain-Barré syndrome can parallel the onset of systemic manifestations of [Zika virus] infection, indicating a so-called parainfectious onset, which suggests that factors different from the known postinfectious mechanisms may be present in [Zika virus]–related Guillain-Barré syndrome,” the authors explained, adding that 20 (48%) of the 42 laboratory-tested subjects had a parainfectious onset.

“RT-PCR testing of urine is a valuable diagnostic tool for the identification of [Zika virus] infection in patients with Guillain-Barré syndrome,” Dr. Parra and her coauthors concluded.

The study was funded by the Bart McLean Fund for Neuroimmunology Research, Johns Hopkins Project Restore, and the Universidad del Valle. Dr. Parra reported no relevant financial disclosures.

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Key clinical point: RT-PCR tests of individuals with Guillain-Barré syndrome show evidence of Zika virus, with urine samples providing the optimal testing medium.

Major finding: 97% of subjects had Zika-like symptoms prior to onset of GBS, and 40% of GBS patients who underwent RT-PCR testing were positive for Zika virus.

Data source: Study of 68 GBS patients from six hospitals in Colombia, with 42 patients undergoing RT-PCR analysis.

Disclosures: Funding provided by the Bart McLean Fund for Neuroimmunology Research, Johns Hopkins Project Restore, and the Universidad del Valle. Dr. Parra reported no relevant financial disclosures.

CDC updates Zika recommendations on preventing sex transmission

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CDC updates Zika recommendations on preventing sex transmission

Federal health officials are advising men who have possibly been exposed to Zika virus to practice safe sex and delay plans for conception for at least 6 months after exposure.

The Centers for Disease Control and Prevention updated its recommendations for preventing sexual transmission of the Zika virus and its preconception guidance, extending the time frame that men should abstain from unprotected sex to prevent transmission.

Previously, only symptomatic men were advised to wait 6 months before trying to conceive a child, while asymptomatic men had to wait only 8 weeks from last possible exposure. Now, men who have been exposed to the virus should either abstain from sex or use a condom to prevent sexual transmission of the disease for at least 6 months, even if they are asymptomatic. Men who are trying to have a child with their partner should also wait at least 6 months.

For now, recommendations for women have not been changed. Women who have been exposed to Zika virus should wait at least 8 weeks after symptom onset (if symptomatic) or last possible exposure to the virus before attempting to conceive. Women who do not plan to become pregnant but live in, or travel to, Zika-endemic regions should either abstain from sex or use the best possible protection available to them (MMWR. 2016 Sep 30. doi: 10.15585/mmwr.mm6539e1).

“Two new reports describe one presumed and one more definitive case of sexual transmission from men with asymptomatic Zika virus infection to female sex partners,” Emily E. Peterson, MD, of the CDC’s Zika response team, and her colleagues wrote in the Morbidity and Mortality Weekly Report. “Among reported cases of sexually transmitted Zika virus infection, the longest reported period between sexual contact that might have transmitted Zika virus and symptom onset was 32-41 days (based on an incubation period of 3-12 days).”

Zika virus can be transmitted through either vaginal, anal, or oral sexual intercourse. While Zika virus RNA decreases over time after the infection passes, it can linger in semen for as long as 188 days after symptom onset, according to the CDC.

For nonpregnant women, Zika virus RNA has been detected in serum for up to 13 days post-onset of symptoms, and for 58 days in whole blood samples. For pregnant women, it can be detected in serum for as long as 10 weeks after the onset of symptoms.

“Detection of Zika virus RNA in blood might not indicate the presence of infectious virus, and thus the potential risk for maternal-fetal Zika virus transmission periconceptionally is unknown,” the researchers wrote.

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Federal health officials are advising men who have possibly been exposed to Zika virus to practice safe sex and delay plans for conception for at least 6 months after exposure.

The Centers for Disease Control and Prevention updated its recommendations for preventing sexual transmission of the Zika virus and its preconception guidance, extending the time frame that men should abstain from unprotected sex to prevent transmission.

Previously, only symptomatic men were advised to wait 6 months before trying to conceive a child, while asymptomatic men had to wait only 8 weeks from last possible exposure. Now, men who have been exposed to the virus should either abstain from sex or use a condom to prevent sexual transmission of the disease for at least 6 months, even if they are asymptomatic. Men who are trying to have a child with their partner should also wait at least 6 months.

For now, recommendations for women have not been changed. Women who have been exposed to Zika virus should wait at least 8 weeks after symptom onset (if symptomatic) or last possible exposure to the virus before attempting to conceive. Women who do not plan to become pregnant but live in, or travel to, Zika-endemic regions should either abstain from sex or use the best possible protection available to them (MMWR. 2016 Sep 30. doi: 10.15585/mmwr.mm6539e1).

“Two new reports describe one presumed and one more definitive case of sexual transmission from men with asymptomatic Zika virus infection to female sex partners,” Emily E. Peterson, MD, of the CDC’s Zika response team, and her colleagues wrote in the Morbidity and Mortality Weekly Report. “Among reported cases of sexually transmitted Zika virus infection, the longest reported period between sexual contact that might have transmitted Zika virus and symptom onset was 32-41 days (based on an incubation period of 3-12 days).”

Zika virus can be transmitted through either vaginal, anal, or oral sexual intercourse. While Zika virus RNA decreases over time after the infection passes, it can linger in semen for as long as 188 days after symptom onset, according to the CDC.

For nonpregnant women, Zika virus RNA has been detected in serum for up to 13 days post-onset of symptoms, and for 58 days in whole blood samples. For pregnant women, it can be detected in serum for as long as 10 weeks after the onset of symptoms.

“Detection of Zika virus RNA in blood might not indicate the presence of infectious virus, and thus the potential risk for maternal-fetal Zika virus transmission periconceptionally is unknown,” the researchers wrote.

[email protected]

Federal health officials are advising men who have possibly been exposed to Zika virus to practice safe sex and delay plans for conception for at least 6 months after exposure.

The Centers for Disease Control and Prevention updated its recommendations for preventing sexual transmission of the Zika virus and its preconception guidance, extending the time frame that men should abstain from unprotected sex to prevent transmission.

Previously, only symptomatic men were advised to wait 6 months before trying to conceive a child, while asymptomatic men had to wait only 8 weeks from last possible exposure. Now, men who have been exposed to the virus should either abstain from sex or use a condom to prevent sexual transmission of the disease for at least 6 months, even if they are asymptomatic. Men who are trying to have a child with their partner should also wait at least 6 months.

For now, recommendations for women have not been changed. Women who have been exposed to Zika virus should wait at least 8 weeks after symptom onset (if symptomatic) or last possible exposure to the virus before attempting to conceive. Women who do not plan to become pregnant but live in, or travel to, Zika-endemic regions should either abstain from sex or use the best possible protection available to them (MMWR. 2016 Sep 30. doi: 10.15585/mmwr.mm6539e1).

“Two new reports describe one presumed and one more definitive case of sexual transmission from men with asymptomatic Zika virus infection to female sex partners,” Emily E. Peterson, MD, of the CDC’s Zika response team, and her colleagues wrote in the Morbidity and Mortality Weekly Report. “Among reported cases of sexually transmitted Zika virus infection, the longest reported period between sexual contact that might have transmitted Zika virus and symptom onset was 32-41 days (based on an incubation period of 3-12 days).”

Zika virus can be transmitted through either vaginal, anal, or oral sexual intercourse. While Zika virus RNA decreases over time after the infection passes, it can linger in semen for as long as 188 days after symptom onset, according to the CDC.

For nonpregnant women, Zika virus RNA has been detected in serum for up to 13 days post-onset of symptoms, and for 58 days in whole blood samples. For pregnant women, it can be detected in serum for as long as 10 weeks after the onset of symptoms.

“Detection of Zika virus RNA in blood might not indicate the presence of infectious virus, and thus the potential risk for maternal-fetal Zika virus transmission periconceptionally is unknown,” the researchers wrote.

[email protected]

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Postnatally acquired Zika infection in children usually mild

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The clinical course of postnatally acquired Zika virus disease in children younger than 18 years is mild and rarely results in severe illness or death, reported Alyson Goodman, MD, and her associates at the Centers for Disease Control and Prevention (CDC), Atlanta.

There were a total of 158 confirmed or probable postnatally acquired Zika virus disease cases among children younger than 18 years reported to the CDC in the United States between January 2015 and July 2016, wrote researchers in a case series that described the epidemiology, clinical findings, and outcomes of the cases (MMWR. 2016 Sep 30;65:1-4).

©Devonyu/Thinkstock

The cases were reported in 30 d ifferent states, and the states with the highest numbers of reported cases were Florida (23%), New York (11%), and California (9%). All patients acquired Zika virus infections during travel to a location where mosquito-borne transmission had been documented, according to researchers.

The median patient age was 14 years, the majority of the patients were female (56%), and five patients were pregnant.

Of Zika’s four primary clinical signs and symptoms, 82% of the pediatric population had a rash, 55% had a fever, 29% had conjunctivitis, and 28% had arthralgia, with 70% of the children presenting with two or more of these symptoms.

Only two children were hospitalized because of their infections. No children were reported to have meningitis, encephalitis, or Guillain-Barré syndrome, and no patients with Zika virus infection died, researchers reported.

This data “corroborates previously published reports suggesting that the clinical course of Zika virus disease is typically mild in children, as it is in adults,” Dr. Goodman and her associates wrote.

Severe disease and death in children with postnatally acquired Zika virus infection are rare, the researchers pointed out, but they encouraged physicians to consider a Zika virus disease diagnosis for children with the four common symptoms and who reside in or traveled to an area with active Zika virus transmission. All Zika virus disease cases should be reported to state health departments.

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On Twitter @jessnicolecraig

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The clinical course of postnatally acquired Zika virus disease in children younger than 18 years is mild and rarely results in severe illness or death, reported Alyson Goodman, MD, and her associates at the Centers for Disease Control and Prevention (CDC), Atlanta.

There were a total of 158 confirmed or probable postnatally acquired Zika virus disease cases among children younger than 18 years reported to the CDC in the United States between January 2015 and July 2016, wrote researchers in a case series that described the epidemiology, clinical findings, and outcomes of the cases (MMWR. 2016 Sep 30;65:1-4).

©Devonyu/Thinkstock

The cases were reported in 30 d ifferent states, and the states with the highest numbers of reported cases were Florida (23%), New York (11%), and California (9%). All patients acquired Zika virus infections during travel to a location where mosquito-borne transmission had been documented, according to researchers.

The median patient age was 14 years, the majority of the patients were female (56%), and five patients were pregnant.

Of Zika’s four primary clinical signs and symptoms, 82% of the pediatric population had a rash, 55% had a fever, 29% had conjunctivitis, and 28% had arthralgia, with 70% of the children presenting with two or more of these symptoms.

Only two children were hospitalized because of their infections. No children were reported to have meningitis, encephalitis, or Guillain-Barré syndrome, and no patients with Zika virus infection died, researchers reported.

This data “corroborates previously published reports suggesting that the clinical course of Zika virus disease is typically mild in children, as it is in adults,” Dr. Goodman and her associates wrote.

Severe disease and death in children with postnatally acquired Zika virus infection are rare, the researchers pointed out, but they encouraged physicians to consider a Zika virus disease diagnosis for children with the four common symptoms and who reside in or traveled to an area with active Zika virus transmission. All Zika virus disease cases should be reported to state health departments.

[email protected]

On Twitter @jessnicolecraig

The clinical course of postnatally acquired Zika virus disease in children younger than 18 years is mild and rarely results in severe illness or death, reported Alyson Goodman, MD, and her associates at the Centers for Disease Control and Prevention (CDC), Atlanta.

There were a total of 158 confirmed or probable postnatally acquired Zika virus disease cases among children younger than 18 years reported to the CDC in the United States between January 2015 and July 2016, wrote researchers in a case series that described the epidemiology, clinical findings, and outcomes of the cases (MMWR. 2016 Sep 30;65:1-4).

©Devonyu/Thinkstock

The cases were reported in 30 d ifferent states, and the states with the highest numbers of reported cases were Florida (23%), New York (11%), and California (9%). All patients acquired Zika virus infections during travel to a location where mosquito-borne transmission had been documented, according to researchers.

The median patient age was 14 years, the majority of the patients were female (56%), and five patients were pregnant.

Of Zika’s four primary clinical signs and symptoms, 82% of the pediatric population had a rash, 55% had a fever, 29% had conjunctivitis, and 28% had arthralgia, with 70% of the children presenting with two or more of these symptoms.

Only two children were hospitalized because of their infections. No children were reported to have meningitis, encephalitis, or Guillain-Barré syndrome, and no patients with Zika virus infection died, researchers reported.

This data “corroborates previously published reports suggesting that the clinical course of Zika virus disease is typically mild in children, as it is in adults,” Dr. Goodman and her associates wrote.

Severe disease and death in children with postnatally acquired Zika virus infection are rare, the researchers pointed out, but they encouraged physicians to consider a Zika virus disease diagnosis for children with the four common symptoms and who reside in or traveled to an area with active Zika virus transmission. All Zika virus disease cases should be reported to state health departments.

[email protected]

On Twitter @jessnicolecraig

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Key clinical point: Postnatally acquired Zika virus disease in children younger than 18 years is mild and rarely results in severe illness or death.

Major finding: Only two children were hospitalized because of their infections, and no children died.

Data source: Case series of 158 confirmed or probable postnatally acquired Zika virus disease cases among children.

Disclosures: The study was funded by the CDC. Author disclosures were not reported.

New chikungunya diagnostic assay proves quick, effective

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A reverse transcription recombinase polymerase amplification (RT-RPA) assay was able to quickly and effectively identify chikungunya virus (CHIKV), according to a study published in PLOS Neglected Tropical Diseases.

Using chikungunya virus RNA samples, the RT-RPA assay detected down to 80 genome copies per reaction within 15 minutes, a time period four to six times faster than other molecular diagnostic techniques, such as reverse transcription-polymerase chain reaction (RT-PCR). In a sensitivity test involving all chikungunya serotypes and various alphaviruses, flaviviruses, and one phlebovirus, the RT-RPA assay identified all virus genotypes, with the only cross-reaction occurring with O’nyong’nyong virus.

CDC/Cynthia Goldsmith

In a test involving 58 plasma samples of suspected chikungunya fever from a trial in Thailand, two real-time RT-PCR tests identified 36 out of 58 samples (62%) as positive for chikungunya. The RT-RPA test successfully detected the virus in all 36 positive samples and did not detect the virus in any of the negative samples, giving a sensitivity and specificity of 100%.

“The CHIKV RPA assay presented here is a promising tool for CHIKV diagnostics at the point of need,” the investigators wrote. “Integration into a multimer or multiplex assay for simultaneous and differential detection of CHIKV, Dengue virus, and Zika virus, as well as an internal positive control would improve outbreak investigations, since the three viruses induce the same clinical picture upon infection and increasingly cocirculate in many parts of the world.”

Find the full study in PLOS Neglected Tropical Diseases (doi: 10.1371/journal.pntd.0004953).

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A reverse transcription recombinase polymerase amplification (RT-RPA) assay was able to quickly and effectively identify chikungunya virus (CHIKV), according to a study published in PLOS Neglected Tropical Diseases.

Using chikungunya virus RNA samples, the RT-RPA assay detected down to 80 genome copies per reaction within 15 minutes, a time period four to six times faster than other molecular diagnostic techniques, such as reverse transcription-polymerase chain reaction (RT-PCR). In a sensitivity test involving all chikungunya serotypes and various alphaviruses, flaviviruses, and one phlebovirus, the RT-RPA assay identified all virus genotypes, with the only cross-reaction occurring with O’nyong’nyong virus.

CDC/Cynthia Goldsmith

In a test involving 58 plasma samples of suspected chikungunya fever from a trial in Thailand, two real-time RT-PCR tests identified 36 out of 58 samples (62%) as positive for chikungunya. The RT-RPA test successfully detected the virus in all 36 positive samples and did not detect the virus in any of the negative samples, giving a sensitivity and specificity of 100%.

“The CHIKV RPA assay presented here is a promising tool for CHIKV diagnostics at the point of need,” the investigators wrote. “Integration into a multimer or multiplex assay for simultaneous and differential detection of CHIKV, Dengue virus, and Zika virus, as well as an internal positive control would improve outbreak investigations, since the three viruses induce the same clinical picture upon infection and increasingly cocirculate in many parts of the world.”

Find the full study in PLOS Neglected Tropical Diseases (doi: 10.1371/journal.pntd.0004953).

[email protected]

A reverse transcription recombinase polymerase amplification (RT-RPA) assay was able to quickly and effectively identify chikungunya virus (CHIKV), according to a study published in PLOS Neglected Tropical Diseases.

Using chikungunya virus RNA samples, the RT-RPA assay detected down to 80 genome copies per reaction within 15 minutes, a time period four to six times faster than other molecular diagnostic techniques, such as reverse transcription-polymerase chain reaction (RT-PCR). In a sensitivity test involving all chikungunya serotypes and various alphaviruses, flaviviruses, and one phlebovirus, the RT-RPA assay identified all virus genotypes, with the only cross-reaction occurring with O’nyong’nyong virus.

CDC/Cynthia Goldsmith

In a test involving 58 plasma samples of suspected chikungunya fever from a trial in Thailand, two real-time RT-PCR tests identified 36 out of 58 samples (62%) as positive for chikungunya. The RT-RPA test successfully detected the virus in all 36 positive samples and did not detect the virus in any of the negative samples, giving a sensitivity and specificity of 100%.

“The CHIKV RPA assay presented here is a promising tool for CHIKV diagnostics at the point of need,” the investigators wrote. “Integration into a multimer or multiplex assay for simultaneous and differential detection of CHIKV, Dengue virus, and Zika virus, as well as an internal positive control would improve outbreak investigations, since the three viruses induce the same clinical picture upon infection and increasingly cocirculate in many parts of the world.”

Find the full study in PLOS Neglected Tropical Diseases (doi: 10.1371/journal.pntd.0004953).

[email protected]

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