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FDA authorizes first commercial Zika test
Photo by Juan D. Alfonso
The US Food and Drug Administration (FDA) has granted Emergency Use Authorization (EUA) for another test designed to detect Zika virus infection.
The test, Zika Virus RNA Qualitative Real-Time RT-PCR test (Zika RT-PCR test), is intended for the qualitative detection of RNA from the Zika virus in human serum specimens from patients meeting criteria for testing outlined by the Centers for Disease Control and Prevention (CDC).
The Zika RT-PCR test is the first test from a commercial laboratory provider to be granted an EUA for testing patients for Zika virus RNA. The test was developed by Focus Diagnostics, Inc., a subsidiary of Quest Diagnostics.
About the EUA
The Zika RT-PCR test has not been FDA cleared or approved. An EUA allows the use of unapproved medical products or unapproved uses of approved medical products in an emergency.
The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.
The FDA issued the EUA for the Zika RT-PCR test based on data submitted by Focus Diagnostics, Inc., and on the US Secretary of Health and Human Services’ (HHS) declaration that circumstances exist to justify the emergency use of in vitro diagnostic tests for the detection of Zika virus and/or diagnosis of Zika virus infection.
This EUA will terminate when the HHS Secretary’s declaration terminates, unless the FDA revokes it sooner.
Until now, the only Zika tests authorized by the FDA under EUA were available from the CDC and were only used in qualified laboratories designated by the CDC. These are the Trioplex Real-time RT-PCR Assay and the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA).
About the test
Quest Diagnostics plans to make the Zika RT-PCR test broadly available for patient testing early in the week of May 2.
The Zika RT-PCR test is intended for use by clinical laboratory personnel qualified by state and federal regulations who have received specific training on the use of the test in qualified laboratories designated by Focus Diagnostics, Inc., and certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) to perform high-complexity tests.
The test can potentially be performed at any CLIA high-complexity laboratory in the Quest Diagnostics network, which includes several dozen CLIA high-complexity labs in the US, including in Toa Baja, Puerto Rico.
Within the US, positive results of this test must be reported to the CDC.
The CDC recommends RT-PCR testing for Zika infection during approximately the first 7 days of the onset of symptoms for certain patients, including:
- Individuals with symptoms suggestive of Zika infection who have traveled within the last 2 weeks to an area with ongoing transmission
- Asymptomatic pregnant women with a history of residence in or travel to areas of active Zika infection
- Asymptomatic pregnant women whose male sexual partners have traveled to or lived in an area of active Zika infection
- Infants born to mothers who live in or traveled to areas with Zika virus transmission during their pregnancy, including both molecular and serologic testing of infants who are being evaluated for evidence of a congenital Zika virus infection.
A negative test result does not preclude infection, and additional serological testing to evaluate the body’s immune response to infection may be considered within 2 to 12 weeks after symptom onset.
For more information on the Zika RT-PCR test, visit www.QuestDiagnostics.com/Zika. 
Photo by Juan D. Alfonso
The US Food and Drug Administration (FDA) has granted Emergency Use Authorization (EUA) for another test designed to detect Zika virus infection.
The test, Zika Virus RNA Qualitative Real-Time RT-PCR test (Zika RT-PCR test), is intended for the qualitative detection of RNA from the Zika virus in human serum specimens from patients meeting criteria for testing outlined by the Centers for Disease Control and Prevention (CDC).
The Zika RT-PCR test is the first test from a commercial laboratory provider to be granted an EUA for testing patients for Zika virus RNA. The test was developed by Focus Diagnostics, Inc., a subsidiary of Quest Diagnostics.
About the EUA
The Zika RT-PCR test has not been FDA cleared or approved. An EUA allows the use of unapproved medical products or unapproved uses of approved medical products in an emergency.
The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.
The FDA issued the EUA for the Zika RT-PCR test based on data submitted by Focus Diagnostics, Inc., and on the US Secretary of Health and Human Services’ (HHS) declaration that circumstances exist to justify the emergency use of in vitro diagnostic tests for the detection of Zika virus and/or diagnosis of Zika virus infection.
This EUA will terminate when the HHS Secretary’s declaration terminates, unless the FDA revokes it sooner.
Until now, the only Zika tests authorized by the FDA under EUA were available from the CDC and were only used in qualified laboratories designated by the CDC. These are the Trioplex Real-time RT-PCR Assay and the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA).
About the test
Quest Diagnostics plans to make the Zika RT-PCR test broadly available for patient testing early in the week of May 2.
The Zika RT-PCR test is intended for use by clinical laboratory personnel qualified by state and federal regulations who have received specific training on the use of the test in qualified laboratories designated by Focus Diagnostics, Inc., and certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) to perform high-complexity tests.
The test can potentially be performed at any CLIA high-complexity laboratory in the Quest Diagnostics network, which includes several dozen CLIA high-complexity labs in the US, including in Toa Baja, Puerto Rico.
Within the US, positive results of this test must be reported to the CDC.
The CDC recommends RT-PCR testing for Zika infection during approximately the first 7 days of the onset of symptoms for certain patients, including:
- Individuals with symptoms suggestive of Zika infection who have traveled within the last 2 weeks to an area with ongoing transmission
- Asymptomatic pregnant women with a history of residence in or travel to areas of active Zika infection
- Asymptomatic pregnant women whose male sexual partners have traveled to or lived in an area of active Zika infection
- Infants born to mothers who live in or traveled to areas with Zika virus transmission during their pregnancy, including both molecular and serologic testing of infants who are being evaluated for evidence of a congenital Zika virus infection.
A negative test result does not preclude infection, and additional serological testing to evaluate the body’s immune response to infection may be considered within 2 to 12 weeks after symptom onset.
For more information on the Zika RT-PCR test, visit www.QuestDiagnostics.com/Zika.
Photo by Juan D. Alfonso
The US Food and Drug Administration (FDA) has granted Emergency Use Authorization (EUA) for another test designed to detect Zika virus infection.
The test, Zika Virus RNA Qualitative Real-Time RT-PCR test (Zika RT-PCR test), is intended for the qualitative detection of RNA from the Zika virus in human serum specimens from patients meeting criteria for testing outlined by the Centers for Disease Control and Prevention (CDC).
The Zika RT-PCR test is the first test from a commercial laboratory provider to be granted an EUA for testing patients for Zika virus RNA. The test was developed by Focus Diagnostics, Inc., a subsidiary of Quest Diagnostics.
About the EUA
The Zika RT-PCR test has not been FDA cleared or approved. An EUA allows the use of unapproved medical products or unapproved uses of approved medical products in an emergency.
The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.
The FDA issued the EUA for the Zika RT-PCR test based on data submitted by Focus Diagnostics, Inc., and on the US Secretary of Health and Human Services’ (HHS) declaration that circumstances exist to justify the emergency use of in vitro diagnostic tests for the detection of Zika virus and/or diagnosis of Zika virus infection.
This EUA will terminate when the HHS Secretary’s declaration terminates, unless the FDA revokes it sooner.
Until now, the only Zika tests authorized by the FDA under EUA were available from the CDC and were only used in qualified laboratories designated by the CDC. These are the Trioplex Real-time RT-PCR Assay and the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA).
About the test
Quest Diagnostics plans to make the Zika RT-PCR test broadly available for patient testing early in the week of May 2.
The Zika RT-PCR test is intended for use by clinical laboratory personnel qualified by state and federal regulations who have received specific training on the use of the test in qualified laboratories designated by Focus Diagnostics, Inc., and certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) to perform high-complexity tests.
The test can potentially be performed at any CLIA high-complexity laboratory in the Quest Diagnostics network, which includes several dozen CLIA high-complexity labs in the US, including in Toa Baja, Puerto Rico.
Within the US, positive results of this test must be reported to the CDC.
The CDC recommends RT-PCR testing for Zika infection during approximately the first 7 days of the onset of symptoms for certain patients, including:
- Individuals with symptoms suggestive of Zika infection who have traveled within the last 2 weeks to an area with ongoing transmission
- Asymptomatic pregnant women with a history of residence in or travel to areas of active Zika infection
- Asymptomatic pregnant women whose male sexual partners have traveled to or lived in an area of active Zika infection
- Infants born to mothers who live in or traveled to areas with Zika virus transmission during their pregnancy, including both molecular and serologic testing of infants who are being evaluated for evidence of a congenital Zika virus infection.
A negative test result does not preclude infection, and additional serological testing to evaluate the body’s immune response to infection may be considered within 2 to 12 weeks after symptom onset.
For more information on the Zika RT-PCR test, visit www.QuestDiagnostics.com/Zika.
Cancer diagnosis linked to mental health disorders
A recent cancer diagnosis is associated with an increased risk for mental health disorders and increased use of psychiatric medications, according to a large, nationwide study conducted in Sweden.
Overall, there was an increased risk of mental health disorders from 10 months before a cancer diagnosis that peaked during the first week after diagnosis and decreased after that, although the risk remained elevated at 10 years after diagnosis.
In addition, there was an increased use of psychiatric medications from 1 month before cancer diagnosis that peaked at about 3 months after diagnosis and remained elevated 2 years after diagnosis.
Donghao Lu, MD, of the Karolinska Institutet in Stockholm, Sweden and colleagues conducted this study and reported the results in JAMA Oncology.
The study included 304,118 patients with cancer and 3,041,174 cancer-free individuals randomly selected from the Swedish population for comparison.
The researchers investigated changes in risk for several common and potentially stress-related mental disorders—including depression, anxiety, substance abuse, somatoform/conversion disorder, and stress reaction/adjustment disorder—from the cancer diagnostic workup through to post-diagnosis.
They found the relative rate for all of the mental disorders studied started to increase from 10 months before cancer diagnosis, with a hazard ratio [HR] of 1.1 (95%CI, 1.1-1.2).
The rate peaked during the first week after diagnosis, with an HR of 6.7 (95%CI, 6.1-7.4). It decreased rapidly thereafter but was still elevated 10 years after diagnosis, with an HR of 1.1 (95%CI, 1.1-1.2).
The rate elevation was clear for all of the main cancers, including hematologic malignancies, except for nonmelanoma skin cancer.
Among the cancer patients, the mental disorder with the highest cumulative incidence was depression. This was followed by anxiety and stress reaction/adjustment disorder.
When compared to controls, the cancer patients had a higher cumulative incidence of most of the mental disorders. The exception was somatoform/conversion disorder.
The researchers also examined the use of psychiatric medications for patients with cancer to assess milder mental health conditions and symptoms.
The team found an increased use of psychiatric medications in cancer patients compared to controls, from 1 month before diagnosis—12.2% vs 11.7% (P=0.04)—that peaked at about 3 months after diagnosis—18.1% vs 11.9% (P<0.001)—and was still elevated 2 years after diagnosis—15.4% vs 12.7% (P<0.001).
The researchers said the results of this study support the existing guidelines of integrating psychological management into cancer care and call for extended vigilance for multiple mental disorders starting from the time of the cancer diagnostic workup.
A recent cancer diagnosis is associated with an increased risk for mental health disorders and increased use of psychiatric medications, according to a large, nationwide study conducted in Sweden.
Overall, there was an increased risk of mental health disorders from 10 months before a cancer diagnosis that peaked during the first week after diagnosis and decreased after that, although the risk remained elevated at 10 years after diagnosis.
In addition, there was an increased use of psychiatric medications from 1 month before cancer diagnosis that peaked at about 3 months after diagnosis and remained elevated 2 years after diagnosis.
Donghao Lu, MD, of the Karolinska Institutet in Stockholm, Sweden and colleagues conducted this study and reported the results in JAMA Oncology.
The study included 304,118 patients with cancer and 3,041,174 cancer-free individuals randomly selected from the Swedish population for comparison.
The researchers investigated changes in risk for several common and potentially stress-related mental disorders—including depression, anxiety, substance abuse, somatoform/conversion disorder, and stress reaction/adjustment disorder—from the cancer diagnostic workup through to post-diagnosis.
They found the relative rate for all of the mental disorders studied started to increase from 10 months before cancer diagnosis, with a hazard ratio [HR] of 1.1 (95%CI, 1.1-1.2).
The rate peaked during the first week after diagnosis, with an HR of 6.7 (95%CI, 6.1-7.4). It decreased rapidly thereafter but was still elevated 10 years after diagnosis, with an HR of 1.1 (95%CI, 1.1-1.2).
The rate elevation was clear for all of the main cancers, including hematologic malignancies, except for nonmelanoma skin cancer.
Among the cancer patients, the mental disorder with the highest cumulative incidence was depression. This was followed by anxiety and stress reaction/adjustment disorder.
When compared to controls, the cancer patients had a higher cumulative incidence of most of the mental disorders. The exception was somatoform/conversion disorder.
The researchers also examined the use of psychiatric medications for patients with cancer to assess milder mental health conditions and symptoms.
The team found an increased use of psychiatric medications in cancer patients compared to controls, from 1 month before diagnosis—12.2% vs 11.7% (P=0.04)—that peaked at about 3 months after diagnosis—18.1% vs 11.9% (P<0.001)—and was still elevated 2 years after diagnosis—15.4% vs 12.7% (P<0.001).
The researchers said the results of this study support the existing guidelines of integrating psychological management into cancer care and call for extended vigilance for multiple mental disorders starting from the time of the cancer diagnostic workup.
A recent cancer diagnosis is associated with an increased risk for mental health disorders and increased use of psychiatric medications, according to a large, nationwide study conducted in Sweden.
Overall, there was an increased risk of mental health disorders from 10 months before a cancer diagnosis that peaked during the first week after diagnosis and decreased after that, although the risk remained elevated at 10 years after diagnosis.
In addition, there was an increased use of psychiatric medications from 1 month before cancer diagnosis that peaked at about 3 months after diagnosis and remained elevated 2 years after diagnosis.
Donghao Lu, MD, of the Karolinska Institutet in Stockholm, Sweden and colleagues conducted this study and reported the results in JAMA Oncology.
The study included 304,118 patients with cancer and 3,041,174 cancer-free individuals randomly selected from the Swedish population for comparison.
The researchers investigated changes in risk for several common and potentially stress-related mental disorders—including depression, anxiety, substance abuse, somatoform/conversion disorder, and stress reaction/adjustment disorder—from the cancer diagnostic workup through to post-diagnosis.
They found the relative rate for all of the mental disorders studied started to increase from 10 months before cancer diagnosis, with a hazard ratio [HR] of 1.1 (95%CI, 1.1-1.2).
The rate peaked during the first week after diagnosis, with an HR of 6.7 (95%CI, 6.1-7.4). It decreased rapidly thereafter but was still elevated 10 years after diagnosis, with an HR of 1.1 (95%CI, 1.1-1.2).
The rate elevation was clear for all of the main cancers, including hematologic malignancies, except for nonmelanoma skin cancer.
Among the cancer patients, the mental disorder with the highest cumulative incidence was depression. This was followed by anxiety and stress reaction/adjustment disorder.
When compared to controls, the cancer patients had a higher cumulative incidence of most of the mental disorders. The exception was somatoform/conversion disorder.
The researchers also examined the use of psychiatric medications for patients with cancer to assess milder mental health conditions and symptoms.
The team found an increased use of psychiatric medications in cancer patients compared to controls, from 1 month before diagnosis—12.2% vs 11.7% (P=0.04)—that peaked at about 3 months after diagnosis—18.1% vs 11.9% (P<0.001)—and was still elevated 2 years after diagnosis—15.4% vs 12.7% (P<0.001).
The researchers said the results of this study support the existing guidelines of integrating psychological management into cancer care and call for extended vigilance for multiple mental disorders starting from the time of the cancer diagnostic workup.
Costs for orally administered cancer drugs on the rise
Photo courtesy of the CDC
New orally administered cancer drugs are much more expensive in their first year on the market than such drugs launched about 15 years ago, according to a study published in JAMA Oncology.
The research showed that a month of treatment with orally administered cancer drugs introduced in 2014 was, on average, 6 times more expensive at launch than monthly treatment costs for such drugs introduced in 2000, after adjusting for inflation.
In addition, most existing therapies had substantial price increases from the time they were launched to 2014.
“The major trend here is that these products are just getting more expensive over time,” said study author Stacie Dusetzina, PhD, of the University of North Carolina at Chapel Hill.
For this study, Dr Dusetzina evaluated what commercial health insurance companies and patients paid for prescription fills—before rebates and discounts—for 32 orally administered cancer drugs from 2000 to 2014. The information came from the TruvenHealth MarketScan Commercial Claims and Encounters database.
The data showed that orally administered drugs approved in 2000 cost an average of $1869 (95% CI, $1648-$2121) per month, compared to $11,325 (95% CI, $10 989-$11 671) for those approved in 2014.
When Dr Dusetzina compared changes in spending by year from a product’s launch to 2014, she observed increases in most of the drugs studied.
The drugs with the largest increases in monthly spending were thalidomide, which increased from $1869 to $7564 ($5695) and imatinib, which increased from $3346 to $8479 ($5133).
However, 2 drugs showed decreases in mean monthly spending between their launch and 2014. Monthly spending for lenalidomide decreased from $10,109 to $9640 ($469), and monthly spending for vorinostat decreased from $9755 to $7592 ($2163).
Dr Dusetzina pointed out that the amount patients pay for these drugs depends on their healthcare benefits. However, the high prices are being passed along to patients more and more, potentially affecting the patients’ access to these drugs.
“Patients are increasingly taking on the burden of paying for these high-cost specialty drugs as plans move toward use of higher deductibles and co-insurance—where a patient will pay a percentage of the drug cost rather than a flat copay,” Dr Dusetzina said.
She noted that while this study did account for payments by commercial health plans, it did not account for spending by Medicaid and Medicare, which may differ. In addition, only the products that were dispensed and reimbursed by commercial health plans were included, which may have excluded rarely used or recently approved products.
Photo courtesy of the CDC
New orally administered cancer drugs are much more expensive in their first year on the market than such drugs launched about 15 years ago, according to a study published in JAMA Oncology.
The research showed that a month of treatment with orally administered cancer drugs introduced in 2014 was, on average, 6 times more expensive at launch than monthly treatment costs for such drugs introduced in 2000, after adjusting for inflation.
In addition, most existing therapies had substantial price increases from the time they were launched to 2014.
“The major trend here is that these products are just getting more expensive over time,” said study author Stacie Dusetzina, PhD, of the University of North Carolina at Chapel Hill.
For this study, Dr Dusetzina evaluated what commercial health insurance companies and patients paid for prescription fills—before rebates and discounts—for 32 orally administered cancer drugs from 2000 to 2014. The information came from the TruvenHealth MarketScan Commercial Claims and Encounters database.
The data showed that orally administered drugs approved in 2000 cost an average of $1869 (95% CI, $1648-$2121) per month, compared to $11,325 (95% CI, $10 989-$11 671) for those approved in 2014.
When Dr Dusetzina compared changes in spending by year from a product’s launch to 2014, she observed increases in most of the drugs studied.
The drugs with the largest increases in monthly spending were thalidomide, which increased from $1869 to $7564 ($5695) and imatinib, which increased from $3346 to $8479 ($5133).
However, 2 drugs showed decreases in mean monthly spending between their launch and 2014. Monthly spending for lenalidomide decreased from $10,109 to $9640 ($469), and monthly spending for vorinostat decreased from $9755 to $7592 ($2163).
Dr Dusetzina pointed out that the amount patients pay for these drugs depends on their healthcare benefits. However, the high prices are being passed along to patients more and more, potentially affecting the patients’ access to these drugs.
“Patients are increasingly taking on the burden of paying for these high-cost specialty drugs as plans move toward use of higher deductibles and co-insurance—where a patient will pay a percentage of the drug cost rather than a flat copay,” Dr Dusetzina said.
She noted that while this study did account for payments by commercial health plans, it did not account for spending by Medicaid and Medicare, which may differ. In addition, only the products that were dispensed and reimbursed by commercial health plans were included, which may have excluded rarely used or recently approved products.
Photo courtesy of the CDC
New orally administered cancer drugs are much more expensive in their first year on the market than such drugs launched about 15 years ago, according to a study published in JAMA Oncology.
The research showed that a month of treatment with orally administered cancer drugs introduced in 2014 was, on average, 6 times more expensive at launch than monthly treatment costs for such drugs introduced in 2000, after adjusting for inflation.
In addition, most existing therapies had substantial price increases from the time they were launched to 2014.
“The major trend here is that these products are just getting more expensive over time,” said study author Stacie Dusetzina, PhD, of the University of North Carolina at Chapel Hill.
For this study, Dr Dusetzina evaluated what commercial health insurance companies and patients paid for prescription fills—before rebates and discounts—for 32 orally administered cancer drugs from 2000 to 2014. The information came from the TruvenHealth MarketScan Commercial Claims and Encounters database.
The data showed that orally administered drugs approved in 2000 cost an average of $1869 (95% CI, $1648-$2121) per month, compared to $11,325 (95% CI, $10 989-$11 671) for those approved in 2014.
When Dr Dusetzina compared changes in spending by year from a product’s launch to 2014, she observed increases in most of the drugs studied.
The drugs with the largest increases in monthly spending were thalidomide, which increased from $1869 to $7564 ($5695) and imatinib, which increased from $3346 to $8479 ($5133).
However, 2 drugs showed decreases in mean monthly spending between their launch and 2014. Monthly spending for lenalidomide decreased from $10,109 to $9640 ($469), and monthly spending for vorinostat decreased from $9755 to $7592 ($2163).
Dr Dusetzina pointed out that the amount patients pay for these drugs depends on their healthcare benefits. However, the high prices are being passed along to patients more and more, potentially affecting the patients’ access to these drugs.
“Patients are increasingly taking on the burden of paying for these high-cost specialty drugs as plans move toward use of higher deductibles and co-insurance—where a patient will pay a percentage of the drug cost rather than a flat copay,” Dr Dusetzina said.
She noted that while this study did account for payments by commercial health plans, it did not account for spending by Medicaid and Medicare, which may differ. In addition, only the products that were dispensed and reimbursed by commercial health plans were included, which may have excluded rarely used or recently approved products.
CDC, OSHA issue guidance to protect workers from Zika virus
Photo by William Weinert
The US Centers for Disease Control and Prevention (CDC) and the Occupational Safety and Health Administration (OSHA) have issued an interim guidance for protecting workers from occupational exposure to the Zika virus.
The guidance is for healthcare and laboratory workers, outdoor workers, mosquito control workers, and business travelers.
It includes recommendations to help protect these workers from mosquito bites and exposure to an infected person’s blood or other body fluids.
The CDC noted that, although Zika virus is primarily spread by infected mosquitoes, exposure to an infected person’s blood or other body fluids may also result in transmission.
So healthcare workers who may be exposed to contaminated blood or other potentially infectious materials from people infected with Zika virus may require additional protection.
Recommendations for healthcare and laboratory workers
Employers and workers in healthcare settings and laboratories should follow standard infection control and biosafety practices (including universal precautions) as appropriate to prevent or minimize the risk of Zika virus transmission.
Standard precautions include, but are not limited to, hand hygiene and the use of personal protective equipment (PPE) to avoid direct contact with blood and other potentially infectious materials, including laboratory specimens/samples. PPE may include gloves, gowns, masks, and eye protection.
Hand hygiene consists of washing with soap and water or using alcohol-based hand rubs containing at least 60% alcohol. Soap and water are best for hands that are visibly soiled. Perform hand hygiene before and after any contact with a patient, after any contact with potentially infectious material, and before putting on and upon removing PPE, including gloves.
Laboratories should ensure that their facilities and practices meet the appropriate Biosafety Level for the type of work being conducted (including the specific biologic agents—in this case, Zika virus) in the laboratory.
Employers should ensure that workers follow workplace standard operating procedures (eg, workplace exposure control plans) and use the engineering controls and work practices available in the workplace to prevent exposure to blood or other potentially infectious materials.
Employers should ensure workers do not bend, recap, or remove contaminated needles or other contaminated sharps. Properly dispose of these items in closable, puncture-resistant, leak-proof, and labeled or color-coded containers. Workers should use sharps with engineered sharps injury protection to avoid sharps-related injuries.
Additional details and recommendations for business travelers, outdoor workers, and mosquito control workers are available in the full guidance document.
The CDC said it will continue to update this guidance based on accumulating evidence. For updates, visit www.cdc.gov/zika.
Photo by William Weinert
The US Centers for Disease Control and Prevention (CDC) and the Occupational Safety and Health Administration (OSHA) have issued an interim guidance for protecting workers from occupational exposure to the Zika virus.
The guidance is for healthcare and laboratory workers, outdoor workers, mosquito control workers, and business travelers.
It includes recommendations to help protect these workers from mosquito bites and exposure to an infected person’s blood or other body fluids.
The CDC noted that, although Zika virus is primarily spread by infected mosquitoes, exposure to an infected person’s blood or other body fluids may also result in transmission.
So healthcare workers who may be exposed to contaminated blood or other potentially infectious materials from people infected with Zika virus may require additional protection.
Recommendations for healthcare and laboratory workers
Employers and workers in healthcare settings and laboratories should follow standard infection control and biosafety practices (including universal precautions) as appropriate to prevent or minimize the risk of Zika virus transmission.
Standard precautions include, but are not limited to, hand hygiene and the use of personal protective equipment (PPE) to avoid direct contact with blood and other potentially infectious materials, including laboratory specimens/samples. PPE may include gloves, gowns, masks, and eye protection.
Hand hygiene consists of washing with soap and water or using alcohol-based hand rubs containing at least 60% alcohol. Soap and water are best for hands that are visibly soiled. Perform hand hygiene before and after any contact with a patient, after any contact with potentially infectious material, and before putting on and upon removing PPE, including gloves.
Laboratories should ensure that their facilities and practices meet the appropriate Biosafety Level for the type of work being conducted (including the specific biologic agents—in this case, Zika virus) in the laboratory.
Employers should ensure that workers follow workplace standard operating procedures (eg, workplace exposure control plans) and use the engineering controls and work practices available in the workplace to prevent exposure to blood or other potentially infectious materials.
Employers should ensure workers do not bend, recap, or remove contaminated needles or other contaminated sharps. Properly dispose of these items in closable, puncture-resistant, leak-proof, and labeled or color-coded containers. Workers should use sharps with engineered sharps injury protection to avoid sharps-related injuries.
Additional details and recommendations for business travelers, outdoor workers, and mosquito control workers are available in the full guidance document.
The CDC said it will continue to update this guidance based on accumulating evidence. For updates, visit www.cdc.gov/zika.
Photo by William Weinert
The US Centers for Disease Control and Prevention (CDC) and the Occupational Safety and Health Administration (OSHA) have issued an interim guidance for protecting workers from occupational exposure to the Zika virus.
The guidance is for healthcare and laboratory workers, outdoor workers, mosquito control workers, and business travelers.
It includes recommendations to help protect these workers from mosquito bites and exposure to an infected person’s blood or other body fluids.
The CDC noted that, although Zika virus is primarily spread by infected mosquitoes, exposure to an infected person’s blood or other body fluids may also result in transmission.
So healthcare workers who may be exposed to contaminated blood or other potentially infectious materials from people infected with Zika virus may require additional protection.
Recommendations for healthcare and laboratory workers
Employers and workers in healthcare settings and laboratories should follow standard infection control and biosafety practices (including universal precautions) as appropriate to prevent or minimize the risk of Zika virus transmission.
Standard precautions include, but are not limited to, hand hygiene and the use of personal protective equipment (PPE) to avoid direct contact with blood and other potentially infectious materials, including laboratory specimens/samples. PPE may include gloves, gowns, masks, and eye protection.
Hand hygiene consists of washing with soap and water or using alcohol-based hand rubs containing at least 60% alcohol. Soap and water are best for hands that are visibly soiled. Perform hand hygiene before and after any contact with a patient, after any contact with potentially infectious material, and before putting on and upon removing PPE, including gloves.
Laboratories should ensure that their facilities and practices meet the appropriate Biosafety Level for the type of work being conducted (including the specific biologic agents—in this case, Zika virus) in the laboratory.
Employers should ensure that workers follow workplace standard operating procedures (eg, workplace exposure control plans) and use the engineering controls and work practices available in the workplace to prevent exposure to blood or other potentially infectious materials.
Employers should ensure workers do not bend, recap, or remove contaminated needles or other contaminated sharps. Properly dispose of these items in closable, puncture-resistant, leak-proof, and labeled or color-coded containers. Workers should use sharps with engineered sharps injury protection to avoid sharps-related injuries.
Additional details and recommendations for business travelers, outdoor workers, and mosquito control workers are available in the full guidance document.
The CDC said it will continue to update this guidance based on accumulating evidence. For updates, visit www.cdc.gov/zika.
Creating a better mouse model
Researchers believe they may have discovered why medical interventions that succeed in mice don’t always translate to the clinic.
The team said the fact that lab mice are raised in pathogen-free environments may contribute to the differences in immune system development between lab mice and humans.
But co-housing lab mice with mice from pet stores can produce “dirty” mouse models that may better reflect the immune systems of adult humans.
David Masopust, PhD, of the University of Minnesota in Minneapolis, and his colleagues described these findings in a letter to Nature.
The researchers first explored immunological differences between lab mice and humans by analyzing cervical tissue specimens from adults of each species.
The team found that lab mice had fewer, less diverse, and less widely distributed memory T cells when compared with humans.
The immune systems of lab mice more closely resembled those of human infants, particularly with regard to the number and tissue distribution of memory T cells.
The researchers performed a similar analysis on tissues from lab mice and from mice found in barn or pet store environments.
The non-lab mice had immune systems more like those of adult humans, which suggests the variation in microbial environment—and not the species difference—could account for the immune system differences.
The researchers then set out to determine if the immune systems of lab mice with little exposure to environmental microbes could change when exposed to a different environment.
They co-housed lab mice with healthy mice raised in a pet store. After 8 weeks, analyses of the lab mice revealed patterns of T cells and other immune system components that more closely matched the pet store mice as well as adult humans.
The researchers said these findings suggest that “dirty” mice may model the human immune system more closely than typical lab mice and could be studied to learn more about the role of environment and genetics in the development of the human immune system.
Researchers believe they may have discovered why medical interventions that succeed in mice don’t always translate to the clinic.
The team said the fact that lab mice are raised in pathogen-free environments may contribute to the differences in immune system development between lab mice and humans.
But co-housing lab mice with mice from pet stores can produce “dirty” mouse models that may better reflect the immune systems of adult humans.
David Masopust, PhD, of the University of Minnesota in Minneapolis, and his colleagues described these findings in a letter to Nature.
The researchers first explored immunological differences between lab mice and humans by analyzing cervical tissue specimens from adults of each species.
The team found that lab mice had fewer, less diverse, and less widely distributed memory T cells when compared with humans.
The immune systems of lab mice more closely resembled those of human infants, particularly with regard to the number and tissue distribution of memory T cells.
The researchers performed a similar analysis on tissues from lab mice and from mice found in barn or pet store environments.
The non-lab mice had immune systems more like those of adult humans, which suggests the variation in microbial environment—and not the species difference—could account for the immune system differences.
The researchers then set out to determine if the immune systems of lab mice with little exposure to environmental microbes could change when exposed to a different environment.
They co-housed lab mice with healthy mice raised in a pet store. After 8 weeks, analyses of the lab mice revealed patterns of T cells and other immune system components that more closely matched the pet store mice as well as adult humans.
The researchers said these findings suggest that “dirty” mice may model the human immune system more closely than typical lab mice and could be studied to learn more about the role of environment and genetics in the development of the human immune system.
Researchers believe they may have discovered why medical interventions that succeed in mice don’t always translate to the clinic.
The team said the fact that lab mice are raised in pathogen-free environments may contribute to the differences in immune system development between lab mice and humans.
But co-housing lab mice with mice from pet stores can produce “dirty” mouse models that may better reflect the immune systems of adult humans.
David Masopust, PhD, of the University of Minnesota in Minneapolis, and his colleagues described these findings in a letter to Nature.
The researchers first explored immunological differences between lab mice and humans by analyzing cervical tissue specimens from adults of each species.
The team found that lab mice had fewer, less diverse, and less widely distributed memory T cells when compared with humans.
The immune systems of lab mice more closely resembled those of human infants, particularly with regard to the number and tissue distribution of memory T cells.
The researchers performed a similar analysis on tissues from lab mice and from mice found in barn or pet store environments.
The non-lab mice had immune systems more like those of adult humans, which suggests the variation in microbial environment—and not the species difference—could account for the immune system differences.
The researchers then set out to determine if the immune systems of lab mice with little exposure to environmental microbes could change when exposed to a different environment.
They co-housed lab mice with healthy mice raised in a pet store. After 8 weeks, analyses of the lab mice revealed patterns of T cells and other immune system components that more closely matched the pet store mice as well as adult humans.
The researchers said these findings suggest that “dirty” mice may model the human immune system more closely than typical lab mice and could be studied to learn more about the role of environment and genetics in the development of the human immune system.
Chronic conditions decrease HRQOL in CCSs
Photo from Dana-Farber/
Boston Children’s Cancer
and Blood Disorders Center
Young adult survivors of childhood cancer tend to have inferior health-related quality of life (HRQOL) when compared to the general population, according to research published in the Journal of the National Cancer Institute.
Childhood cancer survivors (CCSs) ages 18 to 29 reported overall HRQOL similar to that of people from the general population who were in their 40s.
However, CCSs fared better if they did not have chronic health conditions.
“Our findings indicate survivors’ accelerated aging and also help us understand the health-related risks associated with having had cancer as a child,” said study author Lisa Diller, MD, of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and Harvard Medical School in Boston, Massachusetts.
“What’s encouraging is that the lower quality of life scores are associated with chronic disease after treatment, not with a history of pediatric cancer itself. If we can prevent treatment-related conditions by changes in the therapy we use for the cancer, then childhood cancer will become an acute, rather than a chronic, illness.”
Dr Diller and her colleagues used information from the Childhood Cancer Survivor Study to compare CCSs (n=7105) and their siblings (n=372) and information from the Medical Expenditures Panel Survey to make comparisons to the general population (n=12,803).
The researchers estimated health utility, a summary measure of quality of life, in these subjects using the Short Form-6D (SF-6D). A score of “1” indicated perfect health, and a score of “0” indicated death.
Results showed that CCSs had significantly lower SF-6D scores than the general population. The mean scores were 0.77 and 0.81, respectively (P<0.001).
But there were no clinically meaningful differences between the CCSs’ siblings and the general population. Their mean SF-6D scores were 0.80 and 0.81, respectively.
Young adult CCSs ages 18 to 29 had a mean score of 0.78, which was roughly equivalent to that reported for 40-to-49-year-old adults in the general population.
However, the presence or absence of chronic health conditions played a role in HRQOL. CCSs who reported no chronic conditions had SF-6D scores similar to the general population, with a mean score of 0.81.
But CCSs with chronic conditions had scores that matched the scores of chronically ill members of the general population. CCSs with 2 chronic conditions had a mean score of 0.77. Those with 3 or more disabling, severe, or life-threatening conditions had a mean score of 0.70.
“By enabling comparisons to the general population, our findings provide context to better understand how the cancer experience may influence the long-term well-being of survivors,” said study author Jennifer Yeh, PhD, of the Harvard T.H. Chan School of Public Health in Boston.
“This is another way to understand the health challenges survivors face and where to focus efforts to improve the long-term health and quality of life of survivors.”
Photo from Dana-Farber/
Boston Children’s Cancer
and Blood Disorders Center
Young adult survivors of childhood cancer tend to have inferior health-related quality of life (HRQOL) when compared to the general population, according to research published in the Journal of the National Cancer Institute.
Childhood cancer survivors (CCSs) ages 18 to 29 reported overall HRQOL similar to that of people from the general population who were in their 40s.
However, CCSs fared better if they did not have chronic health conditions.
“Our findings indicate survivors’ accelerated aging and also help us understand the health-related risks associated with having had cancer as a child,” said study author Lisa Diller, MD, of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and Harvard Medical School in Boston, Massachusetts.
“What’s encouraging is that the lower quality of life scores are associated with chronic disease after treatment, not with a history of pediatric cancer itself. If we can prevent treatment-related conditions by changes in the therapy we use for the cancer, then childhood cancer will become an acute, rather than a chronic, illness.”
Dr Diller and her colleagues used information from the Childhood Cancer Survivor Study to compare CCSs (n=7105) and their siblings (n=372) and information from the Medical Expenditures Panel Survey to make comparisons to the general population (n=12,803).
The researchers estimated health utility, a summary measure of quality of life, in these subjects using the Short Form-6D (SF-6D). A score of “1” indicated perfect health, and a score of “0” indicated death.
Results showed that CCSs had significantly lower SF-6D scores than the general population. The mean scores were 0.77 and 0.81, respectively (P<0.001).
But there were no clinically meaningful differences between the CCSs’ siblings and the general population. Their mean SF-6D scores were 0.80 and 0.81, respectively.
Young adult CCSs ages 18 to 29 had a mean score of 0.78, which was roughly equivalent to that reported for 40-to-49-year-old adults in the general population.
However, the presence or absence of chronic health conditions played a role in HRQOL. CCSs who reported no chronic conditions had SF-6D scores similar to the general population, with a mean score of 0.81.
But CCSs with chronic conditions had scores that matched the scores of chronically ill members of the general population. CCSs with 2 chronic conditions had a mean score of 0.77. Those with 3 or more disabling, severe, or life-threatening conditions had a mean score of 0.70.
“By enabling comparisons to the general population, our findings provide context to better understand how the cancer experience may influence the long-term well-being of survivors,” said study author Jennifer Yeh, PhD, of the Harvard T.H. Chan School of Public Health in Boston.
“This is another way to understand the health challenges survivors face and where to focus efforts to improve the long-term health and quality of life of survivors.”
Photo from Dana-Farber/
Boston Children’s Cancer
and Blood Disorders Center
Young adult survivors of childhood cancer tend to have inferior health-related quality of life (HRQOL) when compared to the general population, according to research published in the Journal of the National Cancer Institute.
Childhood cancer survivors (CCSs) ages 18 to 29 reported overall HRQOL similar to that of people from the general population who were in their 40s.
However, CCSs fared better if they did not have chronic health conditions.
“Our findings indicate survivors’ accelerated aging and also help us understand the health-related risks associated with having had cancer as a child,” said study author Lisa Diller, MD, of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and Harvard Medical School in Boston, Massachusetts.
“What’s encouraging is that the lower quality of life scores are associated with chronic disease after treatment, not with a history of pediatric cancer itself. If we can prevent treatment-related conditions by changes in the therapy we use for the cancer, then childhood cancer will become an acute, rather than a chronic, illness.”
Dr Diller and her colleagues used information from the Childhood Cancer Survivor Study to compare CCSs (n=7105) and their siblings (n=372) and information from the Medical Expenditures Panel Survey to make comparisons to the general population (n=12,803).
The researchers estimated health utility, a summary measure of quality of life, in these subjects using the Short Form-6D (SF-6D). A score of “1” indicated perfect health, and a score of “0” indicated death.
Results showed that CCSs had significantly lower SF-6D scores than the general population. The mean scores were 0.77 and 0.81, respectively (P<0.001).
But there were no clinically meaningful differences between the CCSs’ siblings and the general population. Their mean SF-6D scores were 0.80 and 0.81, respectively.
Young adult CCSs ages 18 to 29 had a mean score of 0.78, which was roughly equivalent to that reported for 40-to-49-year-old adults in the general population.
However, the presence or absence of chronic health conditions played a role in HRQOL. CCSs who reported no chronic conditions had SF-6D scores similar to the general population, with a mean score of 0.81.
But CCSs with chronic conditions had scores that matched the scores of chronically ill members of the general population. CCSs with 2 chronic conditions had a mean score of 0.77. Those with 3 or more disabling, severe, or life-threatening conditions had a mean score of 0.70.
“By enabling comparisons to the general population, our findings provide context to better understand how the cancer experience may influence the long-term well-being of survivors,” said study author Jennifer Yeh, PhD, of the Harvard T.H. Chan School of Public Health in Boston.
“This is another way to understand the health challenges survivors face and where to focus efforts to improve the long-term health and quality of life of survivors.”
Method detects SNVs better, group says
Researchers have developed a new method for detecting single-nucleotide variants (SNVs) in a single cell, and they believe it could have applications for cancer diagnosis and treatment.
The team said the method, known as Monovar, improves upon current single-cell sequencing (SCS) by more accurately detecting SNVs.
During testing, Monovar identified 28 new somatic SNVs in cells from a patient with acute lymphoblastic leukemia (ALL).
The researchers described Monovar in Nature Methods.
“To improve the SNVs in SCS datasets, we developed Monovar,” said study author Nicholas Navin, PhD, of the University of Texas MD Anderson Cancer Center in Houston.
“Monovar is a novel statistical method able to leverage data from multiple single cells to discover SNVs and provides highly detailed genetic data.”
Dr Navin and his colleagues found Monovar superior to standard algorithms for analyzing cells from previously studied patients with 3 different cancer types.
The team analyzed single cells from a patient with triple-negative breast cancer, a patient with muscle-invasive bladder cancer, and a child with ALL.
In cells from the ALL patient, Monovar discovered 57 somatic mutations, including 28 new somatic SNVs.
The researchers said Monovar identified significant mutations in OR4C3 and GPR107 (all subclones); LRFN5, PKD2L1, and ZNF781 (in subs 2, 4 and 5); DNAH7 (sub 1); LYAR and FMNL1 (sub 2); RGS3 (subs 4 and 5); and ADAMTS13, PRSS3, and PKD2L1 (subs 2-5).
The clonal mutations in OR4C3 and GPR107 and the subclonal mutations in PKD2L1, ADAMTS13, PRSS3, and RGS3 were not identified in the original study of the ALL patient (C Gawad et al. PNAS 2014).
Dr Navin and his colleagues said Monovar could have significant translational applications in cancer diagnosis and treatment, personalized medicine, and prenatal genetic diagnosis, where the accurate detection of SNVs is critical for patient care.
The researchers also believe Monovar could be used for studies in a range of biomedical fields.
“With the recent innovations in SCS methods to analyze thousands of single cells in parallel with RNA analysis, which will soon be extended to DNA analysis, the need for accurate DNA variant detection will continue to grow,” said Ken Chen, PhD, also of MD Anderson Cancer Center.
“Monovar is capable of analyzing large-scale datasets and handling different whole-genome protocols. Therefore, it is well-suited for many types of studies.”
Researchers have developed a new method for detecting single-nucleotide variants (SNVs) in a single cell, and they believe it could have applications for cancer diagnosis and treatment.
The team said the method, known as Monovar, improves upon current single-cell sequencing (SCS) by more accurately detecting SNVs.
During testing, Monovar identified 28 new somatic SNVs in cells from a patient with acute lymphoblastic leukemia (ALL).
The researchers described Monovar in Nature Methods.
“To improve the SNVs in SCS datasets, we developed Monovar,” said study author Nicholas Navin, PhD, of the University of Texas MD Anderson Cancer Center in Houston.
“Monovar is a novel statistical method able to leverage data from multiple single cells to discover SNVs and provides highly detailed genetic data.”
Dr Navin and his colleagues found Monovar superior to standard algorithms for analyzing cells from previously studied patients with 3 different cancer types.
The team analyzed single cells from a patient with triple-negative breast cancer, a patient with muscle-invasive bladder cancer, and a child with ALL.
In cells from the ALL patient, Monovar discovered 57 somatic mutations, including 28 new somatic SNVs.
The researchers said Monovar identified significant mutations in OR4C3 and GPR107 (all subclones); LRFN5, PKD2L1, and ZNF781 (in subs 2, 4 and 5); DNAH7 (sub 1); LYAR and FMNL1 (sub 2); RGS3 (subs 4 and 5); and ADAMTS13, PRSS3, and PKD2L1 (subs 2-5).
The clonal mutations in OR4C3 and GPR107 and the subclonal mutations in PKD2L1, ADAMTS13, PRSS3, and RGS3 were not identified in the original study of the ALL patient (C Gawad et al. PNAS 2014).
Dr Navin and his colleagues said Monovar could have significant translational applications in cancer diagnosis and treatment, personalized medicine, and prenatal genetic diagnosis, where the accurate detection of SNVs is critical for patient care.
The researchers also believe Monovar could be used for studies in a range of biomedical fields.
“With the recent innovations in SCS methods to analyze thousands of single cells in parallel with RNA analysis, which will soon be extended to DNA analysis, the need for accurate DNA variant detection will continue to grow,” said Ken Chen, PhD, also of MD Anderson Cancer Center.
“Monovar is capable of analyzing large-scale datasets and handling different whole-genome protocols. Therefore, it is well-suited for many types of studies.”
Researchers have developed a new method for detecting single-nucleotide variants (SNVs) in a single cell, and they believe it could have applications for cancer diagnosis and treatment.
The team said the method, known as Monovar, improves upon current single-cell sequencing (SCS) by more accurately detecting SNVs.
During testing, Monovar identified 28 new somatic SNVs in cells from a patient with acute lymphoblastic leukemia (ALL).
The researchers described Monovar in Nature Methods.
“To improve the SNVs in SCS datasets, we developed Monovar,” said study author Nicholas Navin, PhD, of the University of Texas MD Anderson Cancer Center in Houston.
“Monovar is a novel statistical method able to leverage data from multiple single cells to discover SNVs and provides highly detailed genetic data.”
Dr Navin and his colleagues found Monovar superior to standard algorithms for analyzing cells from previously studied patients with 3 different cancer types.
The team analyzed single cells from a patient with triple-negative breast cancer, a patient with muscle-invasive bladder cancer, and a child with ALL.
In cells from the ALL patient, Monovar discovered 57 somatic mutations, including 28 new somatic SNVs.
The researchers said Monovar identified significant mutations in OR4C3 and GPR107 (all subclones); LRFN5, PKD2L1, and ZNF781 (in subs 2, 4 and 5); DNAH7 (sub 1); LYAR and FMNL1 (sub 2); RGS3 (subs 4 and 5); and ADAMTS13, PRSS3, and PKD2L1 (subs 2-5).
The clonal mutations in OR4C3 and GPR107 and the subclonal mutations in PKD2L1, ADAMTS13, PRSS3, and RGS3 were not identified in the original study of the ALL patient (C Gawad et al. PNAS 2014).
Dr Navin and his colleagues said Monovar could have significant translational applications in cancer diagnosis and treatment, personalized medicine, and prenatal genetic diagnosis, where the accurate detection of SNVs is critical for patient care.
The researchers also believe Monovar could be used for studies in a range of biomedical fields.
“With the recent innovations in SCS methods to analyze thousands of single cells in parallel with RNA analysis, which will soon be extended to DNA analysis, the need for accurate DNA variant detection will continue to grow,” said Ken Chen, PhD, also of MD Anderson Cancer Center.
“Monovar is capable of analyzing large-scale datasets and handling different whole-genome protocols. Therefore, it is well-suited for many types of studies.”
Team explains CD8 Treg dysfunction
Image by Kathryn T. Iacono
Research published in The Journal of Clinical Investigation provides new insights regarding CD8 regulatory T cells (Tregs).
Investigators found that, in young, healthy individuals, CD8 Tregs suppress the activation and expansion of CD4 T cells.
However, older individuals and patients with a rare form of vasculitis exhibit CD8 Treg dysfunction, which is tied to a drop in production of an enzyme called NADPH oxidase 2 (NOX2).
Cornelia Weyand, MD, of Stanford University Medical Center in California, and her colleagues conducted this research.
First, the team found that CD8 Tregs preferentially take up residence in lymph nodes, the spleen, and other regions where there are huge “armies” of CD4 T cells. This proximity puts the CD8 Tregs in a position to stamp out CD4 T-cell activation early on.
Further experiments demonstrated that CD8 Tregs manufacture copious amounts of NOX2, which they package into tiny membrane-bound packets and transfer to the surfaces of abutting CD4 T cells.
These NOX2-laden packets are then taken up by the CD4 T cells. Inside their new home, the enzymes produce large volumes of highly reactive signaling substances that dial down CD4 T cells’ activation and proliferation.
The investigators noted that contact between CD8 Tregs and CD4 T cells in the early stages of activation shuts down the CD4 T cells’ activity and reduces their proliferation by half or more, even several days after the CD8 Tregs have been removed. Transferring NOX2 alone onto activated CD4 T cells also produces this effect.
Next, the team analyzed blood samples from healthy individuals and observed that CD8 Tregs were only about half as common in blood from people age 60 and older as in blood from 20- to 30-year-olds.
Both CD8 Treg numbers and their ability to suppress CD4 T-cell proliferation declined with advancing age. Experiments traced this to a drop in NOX2 production by older donors’ CD8 Tregs.
The investigators also discovered CD8 Treg failure in giant-cell arteritis (GCA). The team compared blood from GCA patients to blood from age-matched healthy control subjects and from patients with 2 other autoimmune diseases—psoriatic arthritis and small-vessel vasculitis. This revealed a severe deficit among GCA patients in NOX2-producing CD8 Tregs.
“This tells us that the deficit in NOX2-producing CD8 Tregs is specific to GCA, not just driving or driven by inflammation,” Dr Weyand said. “That’s good news for our patients who have this disease, which has been an enigma. Now we know something about what’s causing it.”
The discovery of NOX2 on the surface of CD8 Tregs—but not on other T-cell types—makes them much easier to identify and count, Dr Weyand added.
She and her colleagues are taking advantage of the new-found biomarker to tally CD8 Tregs in patients with age-associated disorders now understood to be driven by chronic inflammation to see if CD8 Treg deficits underlie some of these conditions’ pathology and whether they may be amenable to potential NOX2-restoring treatments.
Image by Kathryn T. Iacono
Research published in The Journal of Clinical Investigation provides new insights regarding CD8 regulatory T cells (Tregs).
Investigators found that, in young, healthy individuals, CD8 Tregs suppress the activation and expansion of CD4 T cells.
However, older individuals and patients with a rare form of vasculitis exhibit CD8 Treg dysfunction, which is tied to a drop in production of an enzyme called NADPH oxidase 2 (NOX2).
Cornelia Weyand, MD, of Stanford University Medical Center in California, and her colleagues conducted this research.
First, the team found that CD8 Tregs preferentially take up residence in lymph nodes, the spleen, and other regions where there are huge “armies” of CD4 T cells. This proximity puts the CD8 Tregs in a position to stamp out CD4 T-cell activation early on.
Further experiments demonstrated that CD8 Tregs manufacture copious amounts of NOX2, which they package into tiny membrane-bound packets and transfer to the surfaces of abutting CD4 T cells.
These NOX2-laden packets are then taken up by the CD4 T cells. Inside their new home, the enzymes produce large volumes of highly reactive signaling substances that dial down CD4 T cells’ activation and proliferation.
The investigators noted that contact between CD8 Tregs and CD4 T cells in the early stages of activation shuts down the CD4 T cells’ activity and reduces their proliferation by half or more, even several days after the CD8 Tregs have been removed. Transferring NOX2 alone onto activated CD4 T cells also produces this effect.
Next, the team analyzed blood samples from healthy individuals and observed that CD8 Tregs were only about half as common in blood from people age 60 and older as in blood from 20- to 30-year-olds.
Both CD8 Treg numbers and their ability to suppress CD4 T-cell proliferation declined with advancing age. Experiments traced this to a drop in NOX2 production by older donors’ CD8 Tregs.
The investigators also discovered CD8 Treg failure in giant-cell arteritis (GCA). The team compared blood from GCA patients to blood from age-matched healthy control subjects and from patients with 2 other autoimmune diseases—psoriatic arthritis and small-vessel vasculitis. This revealed a severe deficit among GCA patients in NOX2-producing CD8 Tregs.
“This tells us that the deficit in NOX2-producing CD8 Tregs is specific to GCA, not just driving or driven by inflammation,” Dr Weyand said. “That’s good news for our patients who have this disease, which has been an enigma. Now we know something about what’s causing it.”
The discovery of NOX2 on the surface of CD8 Tregs—but not on other T-cell types—makes them much easier to identify and count, Dr Weyand added.
She and her colleagues are taking advantage of the new-found biomarker to tally CD8 Tregs in patients with age-associated disorders now understood to be driven by chronic inflammation to see if CD8 Treg deficits underlie some of these conditions’ pathology and whether they may be amenable to potential NOX2-restoring treatments.
Image by Kathryn T. Iacono
Research published in The Journal of Clinical Investigation provides new insights regarding CD8 regulatory T cells (Tregs).
Investigators found that, in young, healthy individuals, CD8 Tregs suppress the activation and expansion of CD4 T cells.
However, older individuals and patients with a rare form of vasculitis exhibit CD8 Treg dysfunction, which is tied to a drop in production of an enzyme called NADPH oxidase 2 (NOX2).
Cornelia Weyand, MD, of Stanford University Medical Center in California, and her colleagues conducted this research.
First, the team found that CD8 Tregs preferentially take up residence in lymph nodes, the spleen, and other regions where there are huge “armies” of CD4 T cells. This proximity puts the CD8 Tregs in a position to stamp out CD4 T-cell activation early on.
Further experiments demonstrated that CD8 Tregs manufacture copious amounts of NOX2, which they package into tiny membrane-bound packets and transfer to the surfaces of abutting CD4 T cells.
These NOX2-laden packets are then taken up by the CD4 T cells. Inside their new home, the enzymes produce large volumes of highly reactive signaling substances that dial down CD4 T cells’ activation and proliferation.
The investigators noted that contact between CD8 Tregs and CD4 T cells in the early stages of activation shuts down the CD4 T cells’ activity and reduces their proliferation by half or more, even several days after the CD8 Tregs have been removed. Transferring NOX2 alone onto activated CD4 T cells also produces this effect.
Next, the team analyzed blood samples from healthy individuals and observed that CD8 Tregs were only about half as common in blood from people age 60 and older as in blood from 20- to 30-year-olds.
Both CD8 Treg numbers and their ability to suppress CD4 T-cell proliferation declined with advancing age. Experiments traced this to a drop in NOX2 production by older donors’ CD8 Tregs.
The investigators also discovered CD8 Treg failure in giant-cell arteritis (GCA). The team compared blood from GCA patients to blood from age-matched healthy control subjects and from patients with 2 other autoimmune diseases—psoriatic arthritis and small-vessel vasculitis. This revealed a severe deficit among GCA patients in NOX2-producing CD8 Tregs.
“This tells us that the deficit in NOX2-producing CD8 Tregs is specific to GCA, not just driving or driven by inflammation,” Dr Weyand said. “That’s good news for our patients who have this disease, which has been an enigma. Now we know something about what’s causing it.”
The discovery of NOX2 on the surface of CD8 Tregs—but not on other T-cell types—makes them much easier to identify and count, Dr Weyand added.
She and her colleagues are taking advantage of the new-found biomarker to tally CD8 Tregs in patients with age-associated disorders now understood to be driven by chronic inflammation to see if CD8 Treg deficits underlie some of these conditions’ pathology and whether they may be amenable to potential NOX2-restoring treatments.
Hybrid drug could treat resistant malaria
Photo by James Gathany
A newly developed hybrid drug can treat malaria that is resistant to other therapies, according to preclinical research.
With previous work, researchers found that chemoreversal agents can re-sensitize resistant malaria parasites to the antimalarial agent chloroquine.
For the current study, the team created hybrid compounds that combine chloroquine and a chemoreversal agent.
One of these compounds, 35, proved particularly active, killing malaria parasites that were resistant to chloroquine and/or artemisinin.
Compound 35 was significantly more effective than chloroquine at killing these resistant strains, which included Hb3 (P<0.001), Dd2 (P<0.001), ARS-233 (P<0.001), ARS-272 (P<0.01), NHP-04559 (P<0.01), NHP04773 (P<0.001), and 7G8 (P<0.01).
In addition, the researchers said compound 35 has a “good therapeutic window” and “favorable drug-like properties,” but they are continuing to refine the compound to make it more effective.
The team noted that malaria drugs and chemoreversal agents have been used to treat drug-resistant malaria before. But this is the first time a hybrid of chloroquine and a newly discovered chemoreversal factor has been used in a single novel molecule for this purpose.
The researchers said a single therapy has several advantages over combination therapy. Besides being more convenient to take, it has less risk of drug-drug interactions, may be better absorbed and distributed in the body, and could result in slower development of new resistant strains of malaria.
Kevin S. W. Tan, PhD, of the National University of Singapore, and his colleagues described this research in Antimicrobial Agents and Chemotherapy.
Photo by James Gathany
A newly developed hybrid drug can treat malaria that is resistant to other therapies, according to preclinical research.
With previous work, researchers found that chemoreversal agents can re-sensitize resistant malaria parasites to the antimalarial agent chloroquine.
For the current study, the team created hybrid compounds that combine chloroquine and a chemoreversal agent.
One of these compounds, 35, proved particularly active, killing malaria parasites that were resistant to chloroquine and/or artemisinin.
Compound 35 was significantly more effective than chloroquine at killing these resistant strains, which included Hb3 (P<0.001), Dd2 (P<0.001), ARS-233 (P<0.001), ARS-272 (P<0.01), NHP-04559 (P<0.01), NHP04773 (P<0.001), and 7G8 (P<0.01).
In addition, the researchers said compound 35 has a “good therapeutic window” and “favorable drug-like properties,” but they are continuing to refine the compound to make it more effective.
The team noted that malaria drugs and chemoreversal agents have been used to treat drug-resistant malaria before. But this is the first time a hybrid of chloroquine and a newly discovered chemoreversal factor has been used in a single novel molecule for this purpose.
The researchers said a single therapy has several advantages over combination therapy. Besides being more convenient to take, it has less risk of drug-drug interactions, may be better absorbed and distributed in the body, and could result in slower development of new resistant strains of malaria.
Kevin S. W. Tan, PhD, of the National University of Singapore, and his colleagues described this research in Antimicrobial Agents and Chemotherapy.
Photo by James Gathany
A newly developed hybrid drug can treat malaria that is resistant to other therapies, according to preclinical research.
With previous work, researchers found that chemoreversal agents can re-sensitize resistant malaria parasites to the antimalarial agent chloroquine.
For the current study, the team created hybrid compounds that combine chloroquine and a chemoreversal agent.
One of these compounds, 35, proved particularly active, killing malaria parasites that were resistant to chloroquine and/or artemisinin.
Compound 35 was significantly more effective than chloroquine at killing these resistant strains, which included Hb3 (P<0.001), Dd2 (P<0.001), ARS-233 (P<0.001), ARS-272 (P<0.01), NHP-04559 (P<0.01), NHP04773 (P<0.001), and 7G8 (P<0.01).
In addition, the researchers said compound 35 has a “good therapeutic window” and “favorable drug-like properties,” but they are continuing to refine the compound to make it more effective.
The team noted that malaria drugs and chemoreversal agents have been used to treat drug-resistant malaria before. But this is the first time a hybrid of chloroquine and a newly discovered chemoreversal factor has been used in a single novel molecule for this purpose.
The researchers said a single therapy has several advantages over combination therapy. Besides being more convenient to take, it has less risk of drug-drug interactions, may be better absorbed and distributed in the body, and could result in slower development of new resistant strains of malaria.
Kevin S. W. Tan, PhD, of the National University of Singapore, and his colleagues described this research in Antimicrobial Agents and Chemotherapy.
Antimalarial resistance can’t be passed on, team says
in mosquito gut
Image by Antoine Nicot
and Jacques Denoyelle
Parasites that develop resistance to the antimalarial drug atovaquone cannot pass this resistance on to their offspring, a new study suggests.
Researchers found that malaria parasites develop resistance to atovaquone via mutations in the mitochondrial cytochrome b complex.
However, these mutations also prevent female parasites from reproducing, so the resistance cannot be passed on to future generations.
Geoff McFadden, PhD, of the University of Melbourne in Victoria, Australia, and his colleagues reported these findings in Science.
“These results are very exciting because the spread of drug resistance is currently destroying our ability to control malaria,” Dr McFadden said.
“We now understand the particular genetic mutation that gave rise to drug resistance in some malaria parasite populations and how it eventually kills them in the mosquito, providing new targets for the development of drugs. So the development of drug resistance may not be a major problem if the resistance cannot spread, meaning the drug atovaquone could be more widely used in malaria control.”
To conduct this study, Dr McFadden and his colleagues analyzed 3 atovaquone-resistant strains of Plasmodium berghei, a malaria parasite that infects rodents. Each strain contained a different mutation in cytochrome b.
The researchers found that 2 of the mutations resulted in developmental defects in the parasite zygotes, and the third mutation resulted in complete infertility in the parasites due to severely impaired female germ cells.
Cross breeding parasites with and without these mutations showed that the mutations are not passed on to offspring. From 44 separate transmission attempts involving 750 mosquito bites, transmission of atovaquone resistance was only observed once, and this mutant was unable to transmit further, despite 7 attempts.
The researchers said it appears that atovaquone-resistant mutations severely impair the lifecycle of the parasites when they are living in mosquito hosts, so these mutations cannot be passed on.
In the human malaria parasite Plasmodium falciparum, the researchers identified similar mutations that impaired the ability of the parasites to infect mosquitos, as well as the number of oocysts produced when infection did occur.
in mosquito gut
Image by Antoine Nicot
and Jacques Denoyelle
Parasites that develop resistance to the antimalarial drug atovaquone cannot pass this resistance on to their offspring, a new study suggests.
Researchers found that malaria parasites develop resistance to atovaquone via mutations in the mitochondrial cytochrome b complex.
However, these mutations also prevent female parasites from reproducing, so the resistance cannot be passed on to future generations.
Geoff McFadden, PhD, of the University of Melbourne in Victoria, Australia, and his colleagues reported these findings in Science.
“These results are very exciting because the spread of drug resistance is currently destroying our ability to control malaria,” Dr McFadden said.
“We now understand the particular genetic mutation that gave rise to drug resistance in some malaria parasite populations and how it eventually kills them in the mosquito, providing new targets for the development of drugs. So the development of drug resistance may not be a major problem if the resistance cannot spread, meaning the drug atovaquone could be more widely used in malaria control.”
To conduct this study, Dr McFadden and his colleagues analyzed 3 atovaquone-resistant strains of Plasmodium berghei, a malaria parasite that infects rodents. Each strain contained a different mutation in cytochrome b.
The researchers found that 2 of the mutations resulted in developmental defects in the parasite zygotes, and the third mutation resulted in complete infertility in the parasites due to severely impaired female germ cells.
Cross breeding parasites with and without these mutations showed that the mutations are not passed on to offspring. From 44 separate transmission attempts involving 750 mosquito bites, transmission of atovaquone resistance was only observed once, and this mutant was unable to transmit further, despite 7 attempts.
The researchers said it appears that atovaquone-resistant mutations severely impair the lifecycle of the parasites when they are living in mosquito hosts, so these mutations cannot be passed on.
In the human malaria parasite Plasmodium falciparum, the researchers identified similar mutations that impaired the ability of the parasites to infect mosquitos, as well as the number of oocysts produced when infection did occur.
in mosquito gut
Image by Antoine Nicot
and Jacques Denoyelle
Parasites that develop resistance to the antimalarial drug atovaquone cannot pass this resistance on to their offspring, a new study suggests.
Researchers found that malaria parasites develop resistance to atovaquone via mutations in the mitochondrial cytochrome b complex.
However, these mutations also prevent female parasites from reproducing, so the resistance cannot be passed on to future generations.
Geoff McFadden, PhD, of the University of Melbourne in Victoria, Australia, and his colleagues reported these findings in Science.
“These results are very exciting because the spread of drug resistance is currently destroying our ability to control malaria,” Dr McFadden said.
“We now understand the particular genetic mutation that gave rise to drug resistance in some malaria parasite populations and how it eventually kills them in the mosquito, providing new targets for the development of drugs. So the development of drug resistance may not be a major problem if the resistance cannot spread, meaning the drug atovaquone could be more widely used in malaria control.”
To conduct this study, Dr McFadden and his colleagues analyzed 3 atovaquone-resistant strains of Plasmodium berghei, a malaria parasite that infects rodents. Each strain contained a different mutation in cytochrome b.
The researchers found that 2 of the mutations resulted in developmental defects in the parasite zygotes, and the third mutation resulted in complete infertility in the parasites due to severely impaired female germ cells.
Cross breeding parasites with and without these mutations showed that the mutations are not passed on to offspring. From 44 separate transmission attempts involving 750 mosquito bites, transmission of atovaquone resistance was only observed once, and this mutant was unable to transmit further, despite 7 attempts.
The researchers said it appears that atovaquone-resistant mutations severely impair the lifecycle of the parasites when they are living in mosquito hosts, so these mutations cannot be passed on.
In the human malaria parasite Plasmodium falciparum, the researchers identified similar mutations that impaired the ability of the parasites to infect mosquitos, as well as the number of oocysts produced when infection did occur.