DENVER – During early 2015, exactly a quarter of all patients seen in U.S. rheumatology practices were diagnosed with rheumatoid arthritis, and among them two-thirds received treatment with a disease modifying nonbiologic drug, based on data from more than 200,000 patients who enrolled in an American College of Rheumatology registry during that time.

That’s an example of some of the data now available in an EHR-based registry run by the ACR and open to participation by any U.S.-based rheumatologist, Kaleb Michaud, PhD, said at the annual meeting of the Spondyloarthritis Research and Treatment Network.

Mitchel L. Zoler/Frontline Medical News

The ACR’s Rheumatology Informatics System for Effectiveness (RISE) is an EHR-based registry of passive reporting that as of July 2016 had enrolled 614,738 U.S. patients treated by 1,284 providers in 213 practices, said Dr. Michaud, codirector of the National Data Bank for Rheumatic Diseases in Wichita, Kan., who works with the ACR on RISE as a volunteer.

Patient participation in RISE more than doubled during the past year, rising from 302,000 participating patients in September 2015. In addition to enrolling even more providers with more patients to participate, RISE’s organizers is also now seeking investigators who can use the data collected in RISE to address useful research questions, he said.

RISE has been designated a qualified clinical data registry (QCDR) by the Centers for Medicare & Medicaid Services. If providers using RISE sign an agreement stating that they want to participate for quality reporting purposes, it then happens automatically. Participating practices also meet Medicare’s meaningful use measure of reporting to a specialty registry. Although most rheumatologists with academic positions already have these opportunities, for community rheumatologists this access is “a perq,” Dr. Michaud said.

As just an example of the data trove accumulating in RISE, Dr, Michaud rattled off some quick figures culled from analysis of the 239,302 RISE patients in 55 U.S. practices who entered the registry during October 2014-September 2015. The patients averaged 59 years of age, three quarters were women, 61% were white, 48% had commercial insurance and 30% were covered through Medicare.

Their most recent diagnosis was rheumatoid arthritis in 25%, unspecified myalgia or myositis in 21%, Sjögren’s syndrome in 7%, systemic lupus erythematosus in 6%, psoriatic arthritis in 6%, spondyloarthritides in 4%, gout in 4%, and several other disorders at rates of 1% or less.

Among the rheumatoid arthritis patients, two-thirds were on a nonbiologic disease modifying drug, led by methotrexate in 65% of this subgroup and hydroxychloroquine in a third of the subgroup. A third of the entire study group was on treatment with a biologic or small-molecule drug. Etanercept (Enbrel) and adalimumab (Humira) led in this category with 8% of patients on each of these two drugs, followed by infliximab (Remicade) in 6%. Other usage rates in this category included abatacept (Orencia) in 4%, and tocilizumab (Actemra) and tofacitinib (Xeljanz) each used in about 2% of rheumatoid arthritis patients.

[email protected]

On Twitter @mitchelzoler

DENVER – During early 2015, exactly a quarter of all patients seen in U.S. rheumatology practices were diagnosed with rheumatoid arthritis, and among them two-thirds received treatment with a disease modifying nonbiologic drug, based on data from more than 200,000 patients who enrolled in an American College of Rheumatology registry during that time.

That’s an example of some of the data now available in an EHR-based registry run by the ACR and open to participation by any U.S.-based rheumatologist, Kaleb Michaud, PhD, said at the annual meeting of the Spondyloarthritis Research and Treatment Network.

Mitchel L. Zoler/Frontline Medical News

The ACR’s Rheumatology Informatics System for Effectiveness (RISE) is an EHR-based registry of passive reporting that as of July 2016 had enrolled 614,738 U.S. patients treated by 1,284 providers in 213 practices, said Dr. Michaud, codirector of the National Data Bank for Rheumatic Diseases in Wichita, Kan., who works with the ACR on RISE as a volunteer.

Patient participation in RISE more than doubled during the past year, rising from 302,000 participating patients in September 2015. In addition to enrolling even more providers with more patients to participate, RISE’s organizers is also now seeking investigators who can use the data collected in RISE to address useful research questions, he said.

RISE has been designated a qualified clinical data registry (QCDR) by the Centers for Medicare & Medicaid Services. If providers using RISE sign an agreement stating that they want to participate for quality reporting purposes, it then happens automatically. Participating practices also meet Medicare’s meaningful use measure of reporting to a specialty registry. Although most rheumatologists with academic positions already have these opportunities, for community rheumatologists this access is “a perq,” Dr. Michaud said.

As just an example of the data trove accumulating in RISE, Dr, Michaud rattled off some quick figures culled from analysis of the 239,302 RISE patients in 55 U.S. practices who entered the registry during October 2014-September 2015. The patients averaged 59 years of age, three quarters were women, 61% were white, 48% had commercial insurance and 30% were covered through Medicare.

Their most recent diagnosis was rheumatoid arthritis in 25%, unspecified myalgia or myositis in 21%, Sjögren’s syndrome in 7%, systemic lupus erythematosus in 6%, psoriatic arthritis in 6%, spondyloarthritides in 4%, gout in 4%, and several other disorders at rates of 1% or less.

Among the rheumatoid arthritis patients, two-thirds were on a nonbiologic disease modifying drug, led by methotrexate in 65% of this subgroup and hydroxychloroquine in a third of the subgroup. A third of the entire study group was on treatment with a biologic or small-molecule drug. Etanercept (Enbrel) and adalimumab (Humira) led in this category with 8% of patients on each of these two drugs, followed by infliximab (Remicade) in 6%. Other usage rates in this category included abatacept (Orencia) in 4%, and tocilizumab (Actemra) and tofacitinib (Xeljanz) each used in about 2% of rheumatoid arthritis patients.

[email protected]

On Twitter @mitchelzoler

DENVER – During early 2015, exactly a quarter of all patients seen in U.S. rheumatology practices were diagnosed with rheumatoid arthritis, and among them two-thirds received treatment with a disease modifying nonbiologic drug, based on data from more than 200,000 patients who enrolled in an American College of Rheumatology registry during that time.

That’s an example of some of the data now available in an EHR-based registry run by the ACR and open to participation by any U.S.-based rheumatologist, Kaleb Michaud, PhD, said at the annual meeting of the Spondyloarthritis Research and Treatment Network.

Mitchel L. Zoler/Frontline Medical News

The ACR’s Rheumatology Informatics System for Effectiveness (RISE) is an EHR-based registry of passive reporting that as of July 2016 had enrolled 614,738 U.S. patients treated by 1,284 providers in 213 practices, said Dr. Michaud, codirector of the National Data Bank for Rheumatic Diseases in Wichita, Kan., who works with the ACR on RISE as a volunteer.

Patient participation in RISE more than doubled during the past year, rising from 302,000 participating patients in September 2015. In addition to enrolling even more providers with more patients to participate, RISE’s organizers is also now seeking investigators who can use the data collected in RISE to address useful research questions, he said.

RISE has been designated a qualified clinical data registry (QCDR) by the Centers for Medicare & Medicaid Services. If providers using RISE sign an agreement stating that they want to participate for quality reporting purposes, it then happens automatically. Participating practices also meet Medicare’s meaningful use measure of reporting to a specialty registry. Although most rheumatologists with academic positions already have these opportunities, for community rheumatologists this access is “a perq,” Dr. Michaud said.

As just an example of the data trove accumulating in RISE, Dr, Michaud rattled off some quick figures culled from analysis of the 239,302 RISE patients in 55 U.S. practices who entered the registry during October 2014-September 2015. The patients averaged 59 years of age, three quarters were women, 61% were white, 48% had commercial insurance and 30% were covered through Medicare.

Their most recent diagnosis was rheumatoid arthritis in 25%, unspecified myalgia or myositis in 21%, Sjögren’s syndrome in 7%, systemic lupus erythematosus in 6%, psoriatic arthritis in 6%, spondyloarthritides in 4%, gout in 4%, and several other disorders at rates of 1% or less.

Among the rheumatoid arthritis patients, two-thirds were on a nonbiologic disease modifying drug, led by methotrexate in 65% of this subgroup and hydroxychloroquine in a third of the subgroup. A third of the entire study group was on treatment with a biologic or small-molecule drug. Etanercept (Enbrel) and adalimumab (Humira) led in this category with 8% of patients on each of these two drugs, followed by infliximab (Remicade) in 6%. Other usage rates in this category included abatacept (Orencia) in 4%, and tocilizumab (Actemra) and tofacitinib (Xeljanz) each used in about 2% of rheumatoid arthritis patients.

[email protected]

On Twitter @mitchelzoler

A model incorporating 17 easily obtainable preoperative variables may help clinicians estimate patients’ risk of developing pneumonia after undergoing coronary artery bypass graft surgery, according to a report published in Annals of Thoracic Surgery.

“This model may be used to inform clinician-patient decision making and to identify opportunities for mitigating a patient’s risk,” said Raymond J. Strobel, a medical student at the University of Michigan, Ann Arbor, and his associates.

American Heart Association

Postoperative pneumonia is the most common hospital-acquired infection following CABG, and it raises mortality risk fourfold and increases length of stay threefold. But reliable estimation of patient risk of post-CABG pneumonia has been difficult because of its low relative incidence – roughly 3% – and because most studies of the disorder are nearly a decade out of date.

To devise a predictive model using current data, Mr. Strobel and his associates assessed numerous potential risk factors and outcomes for 16,084 consecutive patients undergoing CABG at all 33 cardiac centers across Michigan during a 3-year period. They identified 531 cases of post-CABG pneumonia (3.3%) in this cohort.

The investigators performed a univariate analysis to test the associations between pneumonia and numerous factors related to patient demographics, medical history, comorbid diseases, laboratory values, cardiac anatomy, cardiac function, pulmonary function, the CABG procedure, and the institution where the procedure was performed. Variables that were found to be significantly associated with pneumonia (though usually with small absolute magnitudes) were then assessed in a multivariate analysis, which was further refined to create the final model.

The final model includes 17 factors that clearly raise the risk of post-CABG pneumonia. These include an elevated leukocyte count; a decreased hematocrit; older patient age; comorbidities such as peripheral vascular disease, diabetes, and liver disease; markers of pulmonary impairment such as cigarette smoking, the need for home oxygen therapy, and chronic lung disease; markers of cardiac dysfunction such as a recent history of arrhythmia and decreased ejection fraction; and emergency or urgent rather than elective operative status.

“This model performs well and demonstrates robustness across important clinical subgroups and centers,” the investigators said (Ann Thorac Surg. 2016 Jun 1; doi: 10.1016/j.athoracsur.2016.03.074).

In particular, this study identified preoperative leukocytosis to be a significant predictor of post-CABG pneumonia across several subgroups of patients. “We speculate that patients presenting with an elevated white blood cell count before surgery may be mounting an immune response against a pathogen and that the insult of CABG significantly increases their odds of postoperative pneumonia. ... It may be prudent to delay surgery until the source of leukocytosis is satisfactorily investigated, if not identified and treated, or the leukocytosis has otherwise resolved,” Mr. Strobel and his associates noted.

A model incorporating 17 easily obtainable preoperative variables may help clinicians estimate patients’ risk of developing pneumonia after undergoing coronary artery bypass graft surgery, according to a report published in Annals of Thoracic Surgery.

“This model may be used to inform clinician-patient decision making and to identify opportunities for mitigating a patient’s risk,” said Raymond J. Strobel, a medical student at the University of Michigan, Ann Arbor, and his associates.

American Heart Association

Postoperative pneumonia is the most common hospital-acquired infection following CABG, and it raises mortality risk fourfold and increases length of stay threefold. But reliable estimation of patient risk of post-CABG pneumonia has been difficult because of its low relative incidence – roughly 3% – and because most studies of the disorder are nearly a decade out of date.

To devise a predictive model using current data, Mr. Strobel and his associates assessed numerous potential risk factors and outcomes for 16,084 consecutive patients undergoing CABG at all 33 cardiac centers across Michigan during a 3-year period. They identified 531 cases of post-CABG pneumonia (3.3%) in this cohort.

The investigators performed a univariate analysis to test the associations between pneumonia and numerous factors related to patient demographics, medical history, comorbid diseases, laboratory values, cardiac anatomy, cardiac function, pulmonary function, the CABG procedure, and the institution where the procedure was performed. Variables that were found to be significantly associated with pneumonia (though usually with small absolute magnitudes) were then assessed in a multivariate analysis, which was further refined to create the final model.

The final model includes 17 factors that clearly raise the risk of post-CABG pneumonia. These include an elevated leukocyte count; a decreased hematocrit; older patient age; comorbidities such as peripheral vascular disease, diabetes, and liver disease; markers of pulmonary impairment such as cigarette smoking, the need for home oxygen therapy, and chronic lung disease; markers of cardiac dysfunction such as a recent history of arrhythmia and decreased ejection fraction; and emergency or urgent rather than elective operative status.

“This model performs well and demonstrates robustness across important clinical subgroups and centers,” the investigators said (Ann Thorac Surg. 2016 Jun 1; doi: 10.1016/j.athoracsur.2016.03.074).

In particular, this study identified preoperative leukocytosis to be a significant predictor of post-CABG pneumonia across several subgroups of patients. “We speculate that patients presenting with an elevated white blood cell count before surgery may be mounting an immune response against a pathogen and that the insult of CABG significantly increases their odds of postoperative pneumonia. ... It may be prudent to delay surgery until the source of leukocytosis is satisfactorily investigated, if not identified and treated, or the leukocytosis has otherwise resolved,” Mr. Strobel and his associates noted.

A model incorporating 17 easily obtainable preoperative variables may help clinicians estimate patients’ risk of developing pneumonia after undergoing coronary artery bypass graft surgery, according to a report published in Annals of Thoracic Surgery.

“This model may be used to inform clinician-patient decision making and to identify opportunities for mitigating a patient’s risk,” said Raymond J. Strobel, a medical student at the University of Michigan, Ann Arbor, and his associates.

American Heart Association

Postoperative pneumonia is the most common hospital-acquired infection following CABG, and it raises mortality risk fourfold and increases length of stay threefold. But reliable estimation of patient risk of post-CABG pneumonia has been difficult because of its low relative incidence – roughly 3% – and because most studies of the disorder are nearly a decade out of date.

To devise a predictive model using current data, Mr. Strobel and his associates assessed numerous potential risk factors and outcomes for 16,084 consecutive patients undergoing CABG at all 33 cardiac centers across Michigan during a 3-year period. They identified 531 cases of post-CABG pneumonia (3.3%) in this cohort.

The investigators performed a univariate analysis to test the associations between pneumonia and numerous factors related to patient demographics, medical history, comorbid diseases, laboratory values, cardiac anatomy, cardiac function, pulmonary function, the CABG procedure, and the institution where the procedure was performed. Variables that were found to be significantly associated with pneumonia (though usually with small absolute magnitudes) were then assessed in a multivariate analysis, which was further refined to create the final model.

The final model includes 17 factors that clearly raise the risk of post-CABG pneumonia. These include an elevated leukocyte count; a decreased hematocrit; older patient age; comorbidities such as peripheral vascular disease, diabetes, and liver disease; markers of pulmonary impairment such as cigarette smoking, the need for home oxygen therapy, and chronic lung disease; markers of cardiac dysfunction such as a recent history of arrhythmia and decreased ejection fraction; and emergency or urgent rather than elective operative status.

“This model performs well and demonstrates robustness across important clinical subgroups and centers,” the investigators said (Ann Thorac Surg. 2016 Jun 1; doi: 10.1016/j.athoracsur.2016.03.074).

In particular, this study identified preoperative leukocytosis to be a significant predictor of post-CABG pneumonia across several subgroups of patients. “We speculate that patients presenting with an elevated white blood cell count before surgery may be mounting an immune response against a pathogen and that the insult of CABG significantly increases their odds of postoperative pneumonia. ... It may be prudent to delay surgery until the source of leukocytosis is satisfactorily investigated, if not identified and treated, or the leukocytosis has otherwise resolved,” Mr. Strobel and his associates noted.

ORLANDO – Screening urinalysis should be a part of routine care for children and young adults with hemophilia, although the clinical significance of the finding is still unclear, investigators say.

Among 93 boys and young men with hemophilia A or B followed at a hemophilia treatment center, nearly half were found to have hematuria on routine screening, a possible indicator for future renal problems, said Kyle Davis, MD, and Amy Dunn, MD, from the division of hematology at Nationwide Children’s Hospital in Columbus, Ohio.

Neil Osterweil/Frontline Medical News

“It’s not routine for all centers to screen for hematuria, so there is likely a large number of patients that are underrecognized, who have hematuria but we don’t even know it,” Dr. Davis said in an interview at the World Federation of Hemophilia World Congress.

Hematuria is a recognized complication in patients with hemophilia A and B, second only to joint damage in frequency. In addition, adults with hemophilia have been shown to have a higher prevalence of renal disease than the general population, suggesting that hematuria might be a marker or harbinger of later renal disease, the authors proposed in a scientific poster.

The investigators conducted their study as part of a quality improvement program at their center aimed at increasing the frequency of urine screening in patients with hemophilia during annual comprehensive visits.

They looked at urinalysis results collected from all male patients older than 2 years with hemophilia A or B seen at their center from August 2011 through September 2015. They defined hematuria as the presence of three or more red blood cells on at least one urinalysis sample.

They also performed univariate logistic regression to evaluate the association of hematuria with patient age, race, hemophilia type and severity, treatment regimen, and history of inhibitory antibodies.

A total of 93 patients, 67 with hemophilia A and 26 with hemophilia B, were included. In all, 43 patients (47%) were identified as having hematuria, with a median of seven red cells. Hematuria was seen in 37 patients with hemophilia A (55%), and in 6 patients with hemophilia B (23%).

Characteristics associated with risk for hematuria included older age and hemophilia A.

Imaging studies available on 24 of the 93 patients showed renal calculi in 3 patients, minor pelviectasis in 1, and congenital dysplastic left kidney, ureterocele, and right hydroureter in 1 patient.

Dr. Davis and Dr. Dunn said that while screening urinalysis could be considered as a part of routine hemophilia, additional studies are needed to replicate the finding in other treatment centers and to determine whether urinalysis results can be predictive of future renal disease, and if so, whether interventions might help.

“For example, there is the potential that if you recognize hematuria in a patient and that patient is currently on an on-demand treatment process, should we switch to prophylaxis?” Dr Davis said.

Dr. Dunn noted that “certainly there are high-risk populations who should be screened, like our patients who have an active inhibitor or even a tolerized inhibitor. Our data suggest that we ought to be looking a bit more closely at those patients, and perhaps that will help us tease out the cause of this. Can we blame it all on hemophilia, or is there something else going on?”

The study was internally funded. Dr. Davis and Dr. Dunn reported no relevant disclosures.

ORLANDO – Screening urinalysis should be a part of routine care for children and young adults with hemophilia, although the clinical significance of the finding is still unclear, investigators say.

Among 93 boys and young men with hemophilia A or B followed at a hemophilia treatment center, nearly half were found to have hematuria on routine screening, a possible indicator for future renal problems, said Kyle Davis, MD, and Amy Dunn, MD, from the division of hematology at Nationwide Children’s Hospital in Columbus, Ohio.

Neil Osterweil/Frontline Medical News

“It’s not routine for all centers to screen for hematuria, so there is likely a large number of patients that are underrecognized, who have hematuria but we don’t even know it,” Dr. Davis said in an interview at the World Federation of Hemophilia World Congress.

Hematuria is a recognized complication in patients with hemophilia A and B, second only to joint damage in frequency. In addition, adults with hemophilia have been shown to have a higher prevalence of renal disease than the general population, suggesting that hematuria might be a marker or harbinger of later renal disease, the authors proposed in a scientific poster.

The investigators conducted their study as part of a quality improvement program at their center aimed at increasing the frequency of urine screening in patients with hemophilia during annual comprehensive visits.

They looked at urinalysis results collected from all male patients older than 2 years with hemophilia A or B seen at their center from August 2011 through September 2015. They defined hematuria as the presence of three or more red blood cells on at least one urinalysis sample.

They also performed univariate logistic regression to evaluate the association of hematuria with patient age, race, hemophilia type and severity, treatment regimen, and history of inhibitory antibodies.

A total of 93 patients, 67 with hemophilia A and 26 with hemophilia B, were included. In all, 43 patients (47%) were identified as having hematuria, with a median of seven red cells. Hematuria was seen in 37 patients with hemophilia A (55%), and in 6 patients with hemophilia B (23%).

Characteristics associated with risk for hematuria included older age and hemophilia A.

Imaging studies available on 24 of the 93 patients showed renal calculi in 3 patients, minor pelviectasis in 1, and congenital dysplastic left kidney, ureterocele, and right hydroureter in 1 patient.

Dr. Davis and Dr. Dunn said that while screening urinalysis could be considered as a part of routine hemophilia, additional studies are needed to replicate the finding in other treatment centers and to determine whether urinalysis results can be predictive of future renal disease, and if so, whether interventions might help.

“For example, there is the potential that if you recognize hematuria in a patient and that patient is currently on an on-demand treatment process, should we switch to prophylaxis?” Dr Davis said.

Dr. Dunn noted that “certainly there are high-risk populations who should be screened, like our patients who have an active inhibitor or even a tolerized inhibitor. Our data suggest that we ought to be looking a bit more closely at those patients, and perhaps that will help us tease out the cause of this. Can we blame it all on hemophilia, or is there something else going on?”

The study was internally funded. Dr. Davis and Dr. Dunn reported no relevant disclosures.

ORLANDO – Screening urinalysis should be a part of routine care for children and young adults with hemophilia, although the clinical significance of the finding is still unclear, investigators say.

Among 93 boys and young men with hemophilia A or B followed at a hemophilia treatment center, nearly half were found to have hematuria on routine screening, a possible indicator for future renal problems, said Kyle Davis, MD, and Amy Dunn, MD, from the division of hematology at Nationwide Children’s Hospital in Columbus, Ohio.

Neil Osterweil/Frontline Medical News

“It’s not routine for all centers to screen for hematuria, so there is likely a large number of patients that are underrecognized, who have hematuria but we don’t even know it,” Dr. Davis said in an interview at the World Federation of Hemophilia World Congress.

Hematuria is a recognized complication in patients with hemophilia A and B, second only to joint damage in frequency. In addition, adults with hemophilia have been shown to have a higher prevalence of renal disease than the general population, suggesting that hematuria might be a marker or harbinger of later renal disease, the authors proposed in a scientific poster.

The investigators conducted their study as part of a quality improvement program at their center aimed at increasing the frequency of urine screening in patients with hemophilia during annual comprehensive visits.

They looked at urinalysis results collected from all male patients older than 2 years with hemophilia A or B seen at their center from August 2011 through September 2015. They defined hematuria as the presence of three or more red blood cells on at least one urinalysis sample.

They also performed univariate logistic regression to evaluate the association of hematuria with patient age, race, hemophilia type and severity, treatment regimen, and history of inhibitory antibodies.

A total of 93 patients, 67 with hemophilia A and 26 with hemophilia B, were included. In all, 43 patients (47%) were identified as having hematuria, with a median of seven red cells. Hematuria was seen in 37 patients with hemophilia A (55%), and in 6 patients with hemophilia B (23%).

Characteristics associated with risk for hematuria included older age and hemophilia A.

Imaging studies available on 24 of the 93 patients showed renal calculi in 3 patients, minor pelviectasis in 1, and congenital dysplastic left kidney, ureterocele, and right hydroureter in 1 patient.

Dr. Davis and Dr. Dunn said that while screening urinalysis could be considered as a part of routine hemophilia, additional studies are needed to replicate the finding in other treatment centers and to determine whether urinalysis results can be predictive of future renal disease, and if so, whether interventions might help.

“For example, there is the potential that if you recognize hematuria in a patient and that patient is currently on an on-demand treatment process, should we switch to prophylaxis?” Dr Davis said.

Dr. Dunn noted that “certainly there are high-risk populations who should be screened, like our patients who have an active inhibitor or even a tolerized inhibitor. Our data suggest that we ought to be looking a bit more closely at those patients, and perhaps that will help us tease out the cause of this. Can we blame it all on hemophilia, or is there something else going on?”

The study was internally funded. Dr. Davis and Dr. Dunn reported no relevant disclosures.

DURBAN, SOUTH AFRICA – The use of efavirenz in HIV-infected participants in the landmark START trial was associated with significantly increased risk of suicidal behavior, Alejandro Arenas-Pinto, MD, reported at the 21st International AIDS Conference.

“The impact of efavirenz exposure was particularly high in those with a prior psychiatric diagnosis,” according to the infectious diseases specialist. “The message here is that it’s probably just those patients with preexisting neuropsychiatric conditions who are at higher risk of suicidal behavior, according to our data. This supports a recommendation to screen for preexisting depression and other neuropsychiatric conditions before efavirenz initiation.”

Bruce Jancin/Frontline Medical News

START was a clinical practice-transforming randomized trial that established a clear clinical benefit for a strategy of initiating antiretroviral therapy immediately upon diagnosis of HIV infection in asymptomatic adults instead of waiting until their CD4+ count drops below the level of 350 cells/mm³ (N Engl J Med. 2015 Aug 27;373[9]:795-807). Immediate antiretroviral therapy (ART) was associated with a 57% reduction in the risk of the primary outcome, a composite comprised of serious AIDS-defining events, serious non-AIDS adverse events, and all-cause mortality.

Once the results were in, however, Dr. Arenas-Pinto and the other START investigators quickly noticed that suicidal behavior was the second-most-common serious non-AIDS event observed in the study. A total of 57 patients were affected, for a rate of 0.36 events per 100 person-years of follow-up. There were 30 suicide attempts, 16 cases of suicidal ideation, 3 completed suicides, and 1 case each classified as intentional self-injury or self-injurious ideation. A closer look was warranted, said Dr. Arenas-Pinto of University College London.

The investigators next determined that the risk of suicidal behavior was significantly higher in the 3,516 START participants on efavirenz than in the 1,169 subjects on other ART drugs. The risk was 4.2-fold greater in patients who started on efavirenz immediately than in those randomized to begin the drug on a deferred basis. In contrast, suicidal behavior was no more frequent in patients who started on other ART medications immediately than if treatment was deferred.

In a multivariate Cox proportional hazards analysis of predictors of suicidal behavior in patients on efavirenz, the stand-out predictor was prior diagnosis of major depression, bipolar disorder, or schizophrenia or another psychotic disorder, with an associated 12.8-fold increased risk. Heavy alcohol use was associated with a 6.1-fold increased risk and ever having used recreational drugs conferred a 2.9-fold increased risk. In contrast, the risk of suicidal behavior in patients on efavirenz dropped sharply with advancing age.

Efavirenz is a non-nucleoside transcriptase inhibitor marketed as Sustiva, or when incorporated into once-daily, fixed-dose, triple-drug therapy with tenofovir/emtricitabine, as Atripla.

The labeling for efavirenz states that many of the drug’s more common side effects involve the brain. They include dizziness, insomnia, depression, anxiety, nightmares, hallucinations, delusions, and confusion.

The START study was funded by the National Institutes of Health. Dr. Arenas-Pinto reported having no financial conflicts of interest.

[email protected]

DURBAN, SOUTH AFRICA – The use of efavirenz in HIV-infected participants in the landmark START trial was associated with significantly increased risk of suicidal behavior, Alejandro Arenas-Pinto, MD, reported at the 21st International AIDS Conference.

“The impact of efavirenz exposure was particularly high in those with a prior psychiatric diagnosis,” according to the infectious diseases specialist. “The message here is that it’s probably just those patients with preexisting neuropsychiatric conditions who are at higher risk of suicidal behavior, according to our data. This supports a recommendation to screen for preexisting depression and other neuropsychiatric conditions before efavirenz initiation.”

Bruce Jancin/Frontline Medical News

START was a clinical practice-transforming randomized trial that established a clear clinical benefit for a strategy of initiating antiretroviral therapy immediately upon diagnosis of HIV infection in asymptomatic adults instead of waiting until their CD4+ count drops below the level of 350 cells/mm³ (N Engl J Med. 2015 Aug 27;373[9]:795-807). Immediate antiretroviral therapy (ART) was associated with a 57% reduction in the risk of the primary outcome, a composite comprised of serious AIDS-defining events, serious non-AIDS adverse events, and all-cause mortality.

Once the results were in, however, Dr. Arenas-Pinto and the other START investigators quickly noticed that suicidal behavior was the second-most-common serious non-AIDS event observed in the study. A total of 57 patients were affected, for a rate of 0.36 events per 100 person-years of follow-up. There were 30 suicide attempts, 16 cases of suicidal ideation, 3 completed suicides, and 1 case each classified as intentional self-injury or self-injurious ideation. A closer look was warranted, said Dr. Arenas-Pinto of University College London.

The investigators next determined that the risk of suicidal behavior was significantly higher in the 3,516 START participants on efavirenz than in the 1,169 subjects on other ART drugs. The risk was 4.2-fold greater in patients who started on efavirenz immediately than in those randomized to begin the drug on a deferred basis. In contrast, suicidal behavior was no more frequent in patients who started on other ART medications immediately than if treatment was deferred.

In a multivariate Cox proportional hazards analysis of predictors of suicidal behavior in patients on efavirenz, the stand-out predictor was prior diagnosis of major depression, bipolar disorder, or schizophrenia or another psychotic disorder, with an associated 12.8-fold increased risk. Heavy alcohol use was associated with a 6.1-fold increased risk and ever having used recreational drugs conferred a 2.9-fold increased risk. In contrast, the risk of suicidal behavior in patients on efavirenz dropped sharply with advancing age.

Efavirenz is a non-nucleoside transcriptase inhibitor marketed as Sustiva, or when incorporated into once-daily, fixed-dose, triple-drug therapy with tenofovir/emtricitabine, as Atripla.

The labeling for efavirenz states that many of the drug’s more common side effects involve the brain. They include dizziness, insomnia, depression, anxiety, nightmares, hallucinations, delusions, and confusion.

The START study was funded by the National Institutes of Health. Dr. Arenas-Pinto reported having no financial conflicts of interest.

[email protected]

DURBAN, SOUTH AFRICA – The use of efavirenz in HIV-infected participants in the landmark START trial was associated with significantly increased risk of suicidal behavior, Alejandro Arenas-Pinto, MD, reported at the 21st International AIDS Conference.

“The impact of efavirenz exposure was particularly high in those with a prior psychiatric diagnosis,” according to the infectious diseases specialist. “The message here is that it’s probably just those patients with preexisting neuropsychiatric conditions who are at higher risk of suicidal behavior, according to our data. This supports a recommendation to screen for preexisting depression and other neuropsychiatric conditions before efavirenz initiation.”

Bruce Jancin/Frontline Medical News

START was a clinical practice-transforming randomized trial that established a clear clinical benefit for a strategy of initiating antiretroviral therapy immediately upon diagnosis of HIV infection in asymptomatic adults instead of waiting until their CD4+ count drops below the level of 350 cells/mm³ (N Engl J Med. 2015 Aug 27;373[9]:795-807). Immediate antiretroviral therapy (ART) was associated with a 57% reduction in the risk of the primary outcome, a composite comprised of serious AIDS-defining events, serious non-AIDS adverse events, and all-cause mortality.

Once the results were in, however, Dr. Arenas-Pinto and the other START investigators quickly noticed that suicidal behavior was the second-most-common serious non-AIDS event observed in the study. A total of 57 patients were affected, for a rate of 0.36 events per 100 person-years of follow-up. There were 30 suicide attempts, 16 cases of suicidal ideation, 3 completed suicides, and 1 case each classified as intentional self-injury or self-injurious ideation. A closer look was warranted, said Dr. Arenas-Pinto of University College London.

The investigators next determined that the risk of suicidal behavior was significantly higher in the 3,516 START participants on efavirenz than in the 1,169 subjects on other ART drugs. The risk was 4.2-fold greater in patients who started on efavirenz immediately than in those randomized to begin the drug on a deferred basis. In contrast, suicidal behavior was no more frequent in patients who started on other ART medications immediately than if treatment was deferred.

In a multivariate Cox proportional hazards analysis of predictors of suicidal behavior in patients on efavirenz, the stand-out predictor was prior diagnosis of major depression, bipolar disorder, or schizophrenia or another psychotic disorder, with an associated 12.8-fold increased risk. Heavy alcohol use was associated with a 6.1-fold increased risk and ever having used recreational drugs conferred a 2.9-fold increased risk. In contrast, the risk of suicidal behavior in patients on efavirenz dropped sharply with advancing age.

Efavirenz is a non-nucleoside transcriptase inhibitor marketed as Sustiva, or when incorporated into once-daily, fixed-dose, triple-drug therapy with tenofovir/emtricitabine, as Atripla.

The labeling for efavirenz states that many of the drug’s more common side effects involve the brain. They include dizziness, insomnia, depression, anxiety, nightmares, hallucinations, delusions, and confusion.

The START study was funded by the National Institutes of Health. Dr. Arenas-Pinto reported having no financial conflicts of interest.

[email protected]

Boston – Autoinflammatory and autoimmune disorders in children have many overlapping features, but the former represents a malfunction of the innate immune system, and the latter a malfunction of the adaptive immune system. Fevers, skin eruptions, joint pain and swelling, fatigue, and growth failure can occur in both, but it is important to identify the underlying problem, according to Raegan Hunt, MD.

Autoinflammatory disorders can be difficult to detect, so it is important to maintain a high index of suspicion for them, Dr. Hunt of Baylor College of Medicine and Texas Children’s Hospital, Houston, said at the American Academy of Dermatology annual summer meeting.

She discussed five signs of possible autoinflammatory disease in children, as described in a recent report by Hal M. Hoffman, MD, and Lori Broderick, MD, of Children’s Hospital of San Diego, La Jolla, Calif. (J Allergy Clin Immunol. July 2016; 138:3-14)*:

1. More than three episodes of fever over 101 degrees Farenheit with no explained infectious etiology.

2. Having predictable patterns of characteristic course of each episode.

3. Having specific symptoms during episodes, including nonpruritic skin eruptions, joint or bone pain, severe abdominal pain, and conjunctivitis, with no upper respiratory infection symptoms.

4. Episodes may be triggered by specific stimuli, such as cold exposure or vaccines.

5. A family history of autoinflammatory disease or amyloidosis.

The authors “propose that two or more of these might suggest that an autoinflammatory disorder is possible and should be investigated,” Dr. Hunt said.

Dr. Hunt reported having no relevant disclosures.

[email protected]

*Correction, 8/16/16: An earlier version of this article failed to note that Dr. Lori Broderick was a co-investigator in the cited report.

Boston – Autoinflammatory and autoimmune disorders in children have many overlapping features, but the former represents a malfunction of the innate immune system, and the latter a malfunction of the adaptive immune system. Fevers, skin eruptions, joint pain and swelling, fatigue, and growth failure can occur in both, but it is important to identify the underlying problem, according to Raegan Hunt, MD.

Autoinflammatory disorders can be difficult to detect, so it is important to maintain a high index of suspicion for them, Dr. Hunt of Baylor College of Medicine and Texas Children’s Hospital, Houston, said at the American Academy of Dermatology annual summer meeting.

She discussed five signs of possible autoinflammatory disease in children, as described in a recent report by Hal M. Hoffman, MD, and Lori Broderick, MD, of Children’s Hospital of San Diego, La Jolla, Calif. (J Allergy Clin Immunol. July 2016; 138:3-14)*:

1. More than three episodes of fever over 101 degrees Farenheit with no explained infectious etiology.

2. Having predictable patterns of characteristic course of each episode.

3. Having specific symptoms during episodes, including nonpruritic skin eruptions, joint or bone pain, severe abdominal pain, and conjunctivitis, with no upper respiratory infection symptoms.

4. Episodes may be triggered by specific stimuli, such as cold exposure or vaccines.

5. A family history of autoinflammatory disease or amyloidosis.

The authors “propose that two or more of these might suggest that an autoinflammatory disorder is possible and should be investigated,” Dr. Hunt said.

Dr. Hunt reported having no relevant disclosures.

[email protected]

*Correction, 8/16/16: An earlier version of this article failed to note that Dr. Lori Broderick was a co-investigator in the cited report.

Boston – Autoinflammatory and autoimmune disorders in children have many overlapping features, but the former represents a malfunction of the innate immune system, and the latter a malfunction of the adaptive immune system. Fevers, skin eruptions, joint pain and swelling, fatigue, and growth failure can occur in both, but it is important to identify the underlying problem, according to Raegan Hunt, MD.

Autoinflammatory disorders can be difficult to detect, so it is important to maintain a high index of suspicion for them, Dr. Hunt of Baylor College of Medicine and Texas Children’s Hospital, Houston, said at the American Academy of Dermatology annual summer meeting.

She discussed five signs of possible autoinflammatory disease in children, as described in a recent report by Hal M. Hoffman, MD, and Lori Broderick, MD, of Children’s Hospital of San Diego, La Jolla, Calif. (J Allergy Clin Immunol. July 2016; 138:3-14)*:

1. More than three episodes of fever over 101 degrees Farenheit with no explained infectious etiology.

2. Having predictable patterns of characteristic course of each episode.

3. Having specific symptoms during episodes, including nonpruritic skin eruptions, joint or bone pain, severe abdominal pain, and conjunctivitis, with no upper respiratory infection symptoms.

4. Episodes may be triggered by specific stimuli, such as cold exposure or vaccines.

5. A family history of autoinflammatory disease or amyloidosis.

The authors “propose that two or more of these might suggest that an autoinflammatory disorder is possible and should be investigated,” Dr. Hunt said.

Dr. Hunt reported having no relevant disclosures.

[email protected]

*Correction, 8/16/16: An earlier version of this article failed to note that Dr. Lori Broderick was a co-investigator in the cited report.

The normal fungal communities that inhabit healthy skin are much more diverse in children than adults, a new study has discovered.

That diversity dwindles, however, around puberty, when the lipophilic taxa Malassezia surges in abundance. This is probably mediated by the increase in sebaceous gland activation and sebum composition that occurs around sexual maturity, Jay-Hyun Jo, PhD, wrote (J Invest Dermatol. 2016 Jul 28; doi: 10.1016/j.jid.2016.05.130).

The diversity of the childhood mycobiome may also play into the larger prevalence of fungal skin diseases in children, wrote Dr. Jo of the National Cancer Institute.

“Several fungal skin infections (dermatophytoses), such as tinea capitis and tinea corporis, are more frequently seen in children. This epidemiological dichotomy in fungal infections may relate to the physiologic characteristics of younger skin, which appears more permissive to colonization by diverse fungi.”

The researchers used the fungal internal transcribed spacer–1 (ITS1) sequence to pinpoint the taxonomic details of the mycobiome of 14 healthy children and 19 healthy adults. They looked at samples from 10 sites on each subject: the external auditory canal, forehead, occiput, retroauricular crease, back, manubrium, antecubital fossa, inguinal crease, volar forearm, and nares.

Malassezia monopolized the adult samples, constituting 80%-99% of the communities on each skin site. In children, however, Malassezia was much less common, comprising 35%-76% of the samples of each site.

However, children boasted a much more diverse mycobiome. Other constituents included members of the Ascomycota, Aspergillus, Epicoccum, and Phoma taxae. Ascomycota species were found on 40% of samples from children, compared with 9.5% of samples from adults. Children also played host to communities of Epicoccum, Cladosporium, and Cryptococcus.

There were individual variations in diversity, however, the authors noted. “For clinical samples from children, decreased diversity was correlated with increased relative abundance of Malassezia, especially on sebaceous sites. Given the predominance of Malassezia on sebaceous skin, it is possible that reduction in diversity was attributed to relative overexpansion of Malassezia.”

The team also discovered gender differences in the mycobiome of children. The sebaceous skin sites of boys were much more likely to host species of Epicoccum and Cryptococcus. Girls showed an early enrichment of Malassezia. “These results suggested that gender may affect mycobiome structures during sexual maturation.”

“Since Malassezia is an obligatory lipophilic fungus, differential Malassezia abundance might be due to the full activation of sebaceous glands during puberty,” they theorized. “Therefore, it would be intriguing to identify the sebaceous gland activity and sebum signatures during childhood in conjunction with sequence-based mycobiome analysis.”

The National Institutes of Health funded the study. Dr. Jo had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

The normal fungal communities that inhabit healthy skin are much more diverse in children than adults, a new study has discovered.

That diversity dwindles, however, around puberty, when the lipophilic taxa Malassezia surges in abundance. This is probably mediated by the increase in sebaceous gland activation and sebum composition that occurs around sexual maturity, Jay-Hyun Jo, PhD, wrote (J Invest Dermatol. 2016 Jul 28; doi: 10.1016/j.jid.2016.05.130).

The diversity of the childhood mycobiome may also play into the larger prevalence of fungal skin diseases in children, wrote Dr. Jo of the National Cancer Institute.

“Several fungal skin infections (dermatophytoses), such as tinea capitis and tinea corporis, are more frequently seen in children. This epidemiological dichotomy in fungal infections may relate to the physiologic characteristics of younger skin, which appears more permissive to colonization by diverse fungi.”

The researchers used the fungal internal transcribed spacer–1 (ITS1) sequence to pinpoint the taxonomic details of the mycobiome of 14 healthy children and 19 healthy adults. They looked at samples from 10 sites on each subject: the external auditory canal, forehead, occiput, retroauricular crease, back, manubrium, antecubital fossa, inguinal crease, volar forearm, and nares.

Malassezia monopolized the adult samples, constituting 80%-99% of the communities on each skin site. In children, however, Malassezia was much less common, comprising 35%-76% of the samples of each site.

However, children boasted a much more diverse mycobiome. Other constituents included members of the Ascomycota, Aspergillus, Epicoccum, and Phoma taxae. Ascomycota species were found on 40% of samples from children, compared with 9.5% of samples from adults. Children also played host to communities of Epicoccum, Cladosporium, and Cryptococcus.

There were individual variations in diversity, however, the authors noted. “For clinical samples from children, decreased diversity was correlated with increased relative abundance of Malassezia, especially on sebaceous sites. Given the predominance of Malassezia on sebaceous skin, it is possible that reduction in diversity was attributed to relative overexpansion of Malassezia.”

The team also discovered gender differences in the mycobiome of children. The sebaceous skin sites of boys were much more likely to host species of Epicoccum and Cryptococcus. Girls showed an early enrichment of Malassezia. “These results suggested that gender may affect mycobiome structures during sexual maturation.”

“Since Malassezia is an obligatory lipophilic fungus, differential Malassezia abundance might be due to the full activation of sebaceous glands during puberty,” they theorized. “Therefore, it would be intriguing to identify the sebaceous gland activity and sebum signatures during childhood in conjunction with sequence-based mycobiome analysis.”

The National Institutes of Health funded the study. Dr. Jo had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

The normal fungal communities that inhabit healthy skin are much more diverse in children than adults, a new study has discovered.

That diversity dwindles, however, around puberty, when the lipophilic taxa Malassezia surges in abundance. This is probably mediated by the increase in sebaceous gland activation and sebum composition that occurs around sexual maturity, Jay-Hyun Jo, PhD, wrote (J Invest Dermatol. 2016 Jul 28; doi: 10.1016/j.jid.2016.05.130).

The diversity of the childhood mycobiome may also play into the larger prevalence of fungal skin diseases in children, wrote Dr. Jo of the National Cancer Institute.

“Several fungal skin infections (dermatophytoses), such as tinea capitis and tinea corporis, are more frequently seen in children. This epidemiological dichotomy in fungal infections may relate to the physiologic characteristics of younger skin, which appears more permissive to colonization by diverse fungi.”

The researchers used the fungal internal transcribed spacer–1 (ITS1) sequence to pinpoint the taxonomic details of the mycobiome of 14 healthy children and 19 healthy adults. They looked at samples from 10 sites on each subject: the external auditory canal, forehead, occiput, retroauricular crease, back, manubrium, antecubital fossa, inguinal crease, volar forearm, and nares.

Malassezia monopolized the adult samples, constituting 80%-99% of the communities on each skin site. In children, however, Malassezia was much less common, comprising 35%-76% of the samples of each site.

However, children boasted a much more diverse mycobiome. Other constituents included members of the Ascomycota, Aspergillus, Epicoccum, and Phoma taxae. Ascomycota species were found on 40% of samples from children, compared with 9.5% of samples from adults. Children also played host to communities of Epicoccum, Cladosporium, and Cryptococcus.

There were individual variations in diversity, however, the authors noted. “For clinical samples from children, decreased diversity was correlated with increased relative abundance of Malassezia, especially on sebaceous sites. Given the predominance of Malassezia on sebaceous skin, it is possible that reduction in diversity was attributed to relative overexpansion of Malassezia.”

The team also discovered gender differences in the mycobiome of children. The sebaceous skin sites of boys were much more likely to host species of Epicoccum and Cryptococcus. Girls showed an early enrichment of Malassezia. “These results suggested that gender may affect mycobiome structures during sexual maturation.”

“Since Malassezia is an obligatory lipophilic fungus, differential Malassezia abundance might be due to the full activation of sebaceous glands during puberty,” they theorized. “Therefore, it would be intriguing to identify the sebaceous gland activity and sebum signatures during childhood in conjunction with sequence-based mycobiome analysis.”

The National Institutes of Health funded the study. Dr. Jo had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

BOSTON – An investigation into 18 nosocomial Candida auris infections at a tertiary care center in Venezuela showed that isolates of the emerging fungal pathogen obtained during the outbreak were resistant to fluconazole and voriconazole. However, the isolates were intermediately susceptible to amphotericin B and susceptible to 5-fluorocitosine, and demonstrated high susceptibility to the candin antifungal anidulafungin.

Dr. Belinda Calvo, an infectious disease specialist at the University of Maracaibo, Venezuela, and her collaborators reported these findings, related to a 2012-2013 C. auris outbreak at the hospital. Dr. Calvo and her coinvestigators noted that other invasive C. auris outbreaks have been reported in India, Korea, and South Africa, but that “the real prevalence of this organism may be underestimated,” since common rapid microbial identification techniques may misidentify the species.

In a poster session at the annual meeting of the American Society of Microbiology, Dr. Calvo and her collaborators reported that the 18 patients involved in the Venezuelan outbreak were critically ill, of whom 11 were pediatric, and all had central venous catheter placement. All but two of the pediatric patients were neonates, and all had serious underlying morbidities; several had significant congenital anomalies. The median patient age was 26 days (range, 2 days to 72 years), reflecting the high number of neonates affected. One of the adult patients had esophageal carcinoma. Overall, 10/18 patients (56%) had undergone surgical procedures, and all had received antibiotics.

As has been reported in other C. auris outbreaks, isolates from blood cultures of affected individuals were initially reported as C. haemulonii by the Vitek 2 C automated microbial identification system. Molecular identification was completed by sequencing the internal transcribed spacer (ITS) of the rDNA gene, with analysis aided by the National Institutes of Health’s GenBank and the Netherland’s CBS Fungal Diversity Centre , in order to confirm the identity of the fungal isolates as C. auris. Dr. Calvo and her associates were able to generate a dendrogram of the 18 isolates, showing high clonality, a trait shared with other nosocomial C. auris outbreaks.

Susceptibility testing of the C. auris cultured from blood samples of the affected patients showed that fluconazole had a minimum inhibitory concentration to inhibit the growth of 50% of the organisms (MIC₅₀₎ of greater than 64 mcg/mL. For fluconazole, the MIC₉₀, range, and geometric mean were all also above 64 mcg/mL, indicating a high level of resistance. For voriconazole, the MICs, range, and mean were all 4 mcg/mL. For amphotericin B, the MIC₅₀ was 1 mcg/mL, the MIC₉₀ was 2 mcg/mL, the range was 1-2, and the geometric mean was 1.414 mcg/mL.

The high number of pediatric patients affected, as well as early pathogen identification with speedy and appropriate antifungal therapy and prompt removal of central venous catheters, likely contributed to the relatively low 30-day crude mortality rate of 28%, said Dr. Calvo and her coauthors.

“C. auris should be considered an emergent multiresistant species,” wrote Dr. Calbo and her collaborators, noting that the opportunistic pathogen has a “high potential for nosocomial horizontal transmission.”

In June 2016, the Centers for Disease Control issued a clinical alert to U.S. healthcare facilities regarding the global emergence of invasive infections caused by C. auris.

The study authors reported no external sources of funding and no conflicts of interest.

[email protected]

On Twitter @karioakes

BOSTON – An investigation into 18 nosocomial Candida auris infections at a tertiary care center in Venezuela showed that isolates of the emerging fungal pathogen obtained during the outbreak were resistant to fluconazole and voriconazole. However, the isolates were intermediately susceptible to amphotericin B and susceptible to 5-fluorocitosine, and demonstrated high susceptibility to the candin antifungal anidulafungin.

Dr. Belinda Calvo, an infectious disease specialist at the University of Maracaibo, Venezuela, and her collaborators reported these findings, related to a 2012-2013 C. auris outbreak at the hospital. Dr. Calvo and her coinvestigators noted that other invasive C. auris outbreaks have been reported in India, Korea, and South Africa, but that “the real prevalence of this organism may be underestimated,” since common rapid microbial identification techniques may misidentify the species.

In a poster session at the annual meeting of the American Society of Microbiology, Dr. Calvo and her collaborators reported that the 18 patients involved in the Venezuelan outbreak were critically ill, of whom 11 were pediatric, and all had central venous catheter placement. All but two of the pediatric patients were neonates, and all had serious underlying morbidities; several had significant congenital anomalies. The median patient age was 26 days (range, 2 days to 72 years), reflecting the high number of neonates affected. One of the adult patients had esophageal carcinoma. Overall, 10/18 patients (56%) had undergone surgical procedures, and all had received antibiotics.

As has been reported in other C. auris outbreaks, isolates from blood cultures of affected individuals were initially reported as C. haemulonii by the Vitek 2 C automated microbial identification system. Molecular identification was completed by sequencing the internal transcribed spacer (ITS) of the rDNA gene, with analysis aided by the National Institutes of Health’s GenBank and the Netherland’s CBS Fungal Diversity Centre , in order to confirm the identity of the fungal isolates as C. auris. Dr. Calvo and her associates were able to generate a dendrogram of the 18 isolates, showing high clonality, a trait shared with other nosocomial C. auris outbreaks.

Susceptibility testing of the C. auris cultured from blood samples of the affected patients showed that fluconazole had a minimum inhibitory concentration to inhibit the growth of 50% of the organisms (MIC₅₀₎ of greater than 64 mcg/mL. For fluconazole, the MIC₉₀, range, and geometric mean were all also above 64 mcg/mL, indicating a high level of resistance. For voriconazole, the MICs, range, and mean were all 4 mcg/mL. For amphotericin B, the MIC₅₀ was 1 mcg/mL, the MIC₉₀ was 2 mcg/mL, the range was 1-2, and the geometric mean was 1.414 mcg/mL.

The high number of pediatric patients affected, as well as early pathogen identification with speedy and appropriate antifungal therapy and prompt removal of central venous catheters, likely contributed to the relatively low 30-day crude mortality rate of 28%, said Dr. Calvo and her coauthors.

“C. auris should be considered an emergent multiresistant species,” wrote Dr. Calbo and her collaborators, noting that the opportunistic pathogen has a “high potential for nosocomial horizontal transmission.”

In June 2016, the Centers for Disease Control issued a clinical alert to U.S. healthcare facilities regarding the global emergence of invasive infections caused by C. auris.

The study authors reported no external sources of funding and no conflicts of interest.

[email protected]

On Twitter @karioakes

BOSTON – An investigation into 18 nosocomial Candida auris infections at a tertiary care center in Venezuela showed that isolates of the emerging fungal pathogen obtained during the outbreak were resistant to fluconazole and voriconazole. However, the isolates were intermediately susceptible to amphotericin B and susceptible to 5-fluorocitosine, and demonstrated high susceptibility to the candin antifungal anidulafungin.

Dr. Belinda Calvo, an infectious disease specialist at the University of Maracaibo, Venezuela, and her collaborators reported these findings, related to a 2012-2013 C. auris outbreak at the hospital. Dr. Calvo and her coinvestigators noted that other invasive C. auris outbreaks have been reported in India, Korea, and South Africa, but that “the real prevalence of this organism may be underestimated,” since common rapid microbial identification techniques may misidentify the species.

In a poster session at the annual meeting of the American Society of Microbiology, Dr. Calvo and her collaborators reported that the 18 patients involved in the Venezuelan outbreak were critically ill, of whom 11 were pediatric, and all had central venous catheter placement. All but two of the pediatric patients were neonates, and all had serious underlying morbidities; several had significant congenital anomalies. The median patient age was 26 days (range, 2 days to 72 years), reflecting the high number of neonates affected. One of the adult patients had esophageal carcinoma. Overall, 10/18 patients (56%) had undergone surgical procedures, and all had received antibiotics.

As has been reported in other C. auris outbreaks, isolates from blood cultures of affected individuals were initially reported as C. haemulonii by the Vitek 2 C automated microbial identification system. Molecular identification was completed by sequencing the internal transcribed spacer (ITS) of the rDNA gene, with analysis aided by the National Institutes of Health’s GenBank and the Netherland’s CBS Fungal Diversity Centre , in order to confirm the identity of the fungal isolates as C. auris. Dr. Calvo and her associates were able to generate a dendrogram of the 18 isolates, showing high clonality, a trait shared with other nosocomial C. auris outbreaks.

Susceptibility testing of the C. auris cultured from blood samples of the affected patients showed that fluconazole had a minimum inhibitory concentration to inhibit the growth of 50% of the organisms (MIC₅₀₎ of greater than 64 mcg/mL. For fluconazole, the MIC₉₀, range, and geometric mean were all also above 64 mcg/mL, indicating a high level of resistance. For voriconazole, the MICs, range, and mean were all 4 mcg/mL. For amphotericin B, the MIC₅₀ was 1 mcg/mL, the MIC₉₀ was 2 mcg/mL, the range was 1-2, and the geometric mean was 1.414 mcg/mL.

The high number of pediatric patients affected, as well as early pathogen identification with speedy and appropriate antifungal therapy and prompt removal of central venous catheters, likely contributed to the relatively low 30-day crude mortality rate of 28%, said Dr. Calvo and her coauthors.

“C. auris should be considered an emergent multiresistant species,” wrote Dr. Calbo and her collaborators, noting that the opportunistic pathogen has a “high potential for nosocomial horizontal transmission.”

In June 2016, the Centers for Disease Control issued a clinical alert to U.S. healthcare facilities regarding the global emergence of invasive infections caused by C. auris.

The study authors reported no external sources of funding and no conflicts of interest.

[email protected]

On Twitter @karioakes

SAN DIEGO – The former president of the Endocrine Society told diabetes educators that it’s time to replace the much-used hemoglobin A_1c level with a measurement that better reflects how diabetes patients are faring.

The problem is that the HbA_1c is “woefully inadequate,” said Robert Vigersky, MD, the medical director of Medtronic Diabetes and president of the Endocrine Society in 2009-2010. “It doesn’t tell you about time-in-range or the frequency, duration, and severity of hypoglycemia or hyperglycemia. And there’s nothing about glycemic variability.”

These measurements are important, he told an audience at the annual meeting of the American Association of Diabetes Educators. For example, “there are several new classes of medication and new technologies. Some decrease HbA_1c with no effect on hypoglycemia. Some affect hypoglycemia with no effect on HbA_1c. How do we think about these globally and compare them to one another?”

To shed more light on the true condition of patients, he said, it’s time to “change the conversation from HbA_1c alone to one that is more glucose-centric. It’s about thinking about glucose as a vital sign, not HbA_1c. This may help health care providers, regulators, and payers better understand what is best for patients.”

He is also thinking about going beyond sugar levels. “Maybe a future composite metric will have more than just glucose numbers,” he said.

Indeed, last hear Dr. Vigersky proposed a composite metric known as “the hypoglycemia-A1C score” that can also take factors like weight, quality of life and costs into account (J Diabetes Sci Technol. 2015 Feb 19;9[5]:1148-51).

But he acknowledged there are challenges. For one, there are at least a dozen different ways to measure hypoglycemia, he said, “and every paper cherry-picks the method they want to show their data in the best light.”

It’s also not clear how best to represent the data once researchers figure out which statistics should be included. Should the overall measurement be a single number? Or should there be multiple numbers? In that case, should the numbers be represented graphically?

Dr. Vigersky said he is working on an approach that illustrates various measurements through a pentagon shape. Its appearance reflects measurements such as mean glucose and duration of high glucose.

However, he predicted the future will produce a simpler measurement: “a multicomponent single value.”

What’s next? “We need to educate the payers about how we can’t stay with HbA_1c. This will take an effort with professional societies. Once everyone agrees, we need to get some consensus about what the elements of the composite metric are.”

Dr. Vigersky is hopeful that the HbA_1c is on its way out, although he acknowledges that it won’t be a rapid process. “It took 20 or more years for everyone to buy into A1C and understand what it represented,” he said. “Changing the conversation isn’t going to happen overnight. But unless we start to address it, it will never happen.”

Dr. Vigersky reported having no relevant financial disclosures.

SAN DIEGO – The former president of the Endocrine Society told diabetes educators that it’s time to replace the much-used hemoglobin A_1c level with a measurement that better reflects how diabetes patients are faring.

The problem is that the HbA_1c is “woefully inadequate,” said Robert Vigersky, MD, the medical director of Medtronic Diabetes and president of the Endocrine Society in 2009-2010. “It doesn’t tell you about time-in-range or the frequency, duration, and severity of hypoglycemia or hyperglycemia. And there’s nothing about glycemic variability.”

These measurements are important, he told an audience at the annual meeting of the American Association of Diabetes Educators. For example, “there are several new classes of medication and new technologies. Some decrease HbA_1c with no effect on hypoglycemia. Some affect hypoglycemia with no effect on HbA_1c. How do we think about these globally and compare them to one another?”

To shed more light on the true condition of patients, he said, it’s time to “change the conversation from HbA_1c alone to one that is more glucose-centric. It’s about thinking about glucose as a vital sign, not HbA_1c. This may help health care providers, regulators, and payers better understand what is best for patients.”

He is also thinking about going beyond sugar levels. “Maybe a future composite metric will have more than just glucose numbers,” he said.

Indeed, last hear Dr. Vigersky proposed a composite metric known as “the hypoglycemia-A1C score” that can also take factors like weight, quality of life and costs into account (J Diabetes Sci Technol. 2015 Feb 19;9[5]:1148-51).

But he acknowledged there are challenges. For one, there are at least a dozen different ways to measure hypoglycemia, he said, “and every paper cherry-picks the method they want to show their data in the best light.”

It’s also not clear how best to represent the data once researchers figure out which statistics should be included. Should the overall measurement be a single number? Or should there be multiple numbers? In that case, should the numbers be represented graphically?

Dr. Vigersky said he is working on an approach that illustrates various measurements through a pentagon shape. Its appearance reflects measurements such as mean glucose and duration of high glucose.

However, he predicted the future will produce a simpler measurement: “a multicomponent single value.”

What’s next? “We need to educate the payers about how we can’t stay with HbA_1c. This will take an effort with professional societies. Once everyone agrees, we need to get some consensus about what the elements of the composite metric are.”

Dr. Vigersky is hopeful that the HbA_1c is on its way out, although he acknowledges that it won’t be a rapid process. “It took 20 or more years for everyone to buy into A1C and understand what it represented,” he said. “Changing the conversation isn’t going to happen overnight. But unless we start to address it, it will never happen.”

Dr. Vigersky reported having no relevant financial disclosures.

SAN DIEGO – The former president of the Endocrine Society told diabetes educators that it’s time to replace the much-used hemoglobin A_1c level with a measurement that better reflects how diabetes patients are faring.

The problem is that the HbA_1c is “woefully inadequate,” said Robert Vigersky, MD, the medical director of Medtronic Diabetes and president of the Endocrine Society in 2009-2010. “It doesn’t tell you about time-in-range or the frequency, duration, and severity of hypoglycemia or hyperglycemia. And there’s nothing about glycemic variability.”

These measurements are important, he told an audience at the annual meeting of the American Association of Diabetes Educators. For example, “there are several new classes of medication and new technologies. Some decrease HbA_1c with no effect on hypoglycemia. Some affect hypoglycemia with no effect on HbA_1c. How do we think about these globally and compare them to one another?”

To shed more light on the true condition of patients, he said, it’s time to “change the conversation from HbA_1c alone to one that is more glucose-centric. It’s about thinking about glucose as a vital sign, not HbA_1c. This may help health care providers, regulators, and payers better understand what is best for patients.”

He is also thinking about going beyond sugar levels. “Maybe a future composite metric will have more than just glucose numbers,” he said.

Indeed, last hear Dr. Vigersky proposed a composite metric known as “the hypoglycemia-A1C score” that can also take factors like weight, quality of life and costs into account (J Diabetes Sci Technol. 2015 Feb 19;9[5]:1148-51).

But he acknowledged there are challenges. For one, there are at least a dozen different ways to measure hypoglycemia, he said, “and every paper cherry-picks the method they want to show their data in the best light.”

It’s also not clear how best to represent the data once researchers figure out which statistics should be included. Should the overall measurement be a single number? Or should there be multiple numbers? In that case, should the numbers be represented graphically?

Dr. Vigersky said he is working on an approach that illustrates various measurements through a pentagon shape. Its appearance reflects measurements such as mean glucose and duration of high glucose.

However, he predicted the future will produce a simpler measurement: “a multicomponent single value.”

What’s next? “We need to educate the payers about how we can’t stay with HbA_1c. This will take an effort with professional societies. Once everyone agrees, we need to get some consensus about what the elements of the composite metric are.”

Dr. Vigersky is hopeful that the HbA_1c is on its way out, although he acknowledges that it won’t be a rapid process. “It took 20 or more years for everyone to buy into A1C and understand what it represented,” he said. “Changing the conversation isn’t going to happen overnight. But unless we start to address it, it will never happen.”

Dr. Vigersky reported having no relevant financial disclosures.

MINNEAPOLIS – The first study to evaluate tofacitinib’s effectiveness at treating severe alopecia areata in the pediatric population found that the janus kinase inhibitor was effective for more than half of the patients, and well tolerated by all.

Of a case series of 13 pediatric patients who had alopecia areata (AA) and were treated with tofacitinib, 9 (68%) experienced “clinically significant” regrowth of hair, with mean improvement in the Severity of Alopecia Tool (SALT) score of 88% for these responders. The nonresponding group, all of whom had alopecia universalis or totalis, saw essentially no response, with a 1% reduction in SALT score.

Lucy Y. Liu, a medical student at Yale University, New Haven, Conn., presented the findings at the annual meeting of the Society for Pediatric Dermatology.

Ms. Liu and her coinvestigators reported that all of the patients had severe AA by SALT scoring, with an overall mean pretreatment SALT score of 74. Eight of the patients (62%) had alopecia universalis, and two (15%) had alopecia totalis.

The patients ranged in age from 12 to 17 years, with a median age of 15. All but three were male, and patients were an average 9 years old at onset of AA. For patients with alopecia totalis or universalis, the duration of the current episode was a median 1.75 years.

Five patients (38%) had atopic dermatitis, while 1 (8%) had thyroid disease. Three patients (23%) had family members with AA; all but one patient, however, had a family history of autoimmune disease of some sort.

Patients were given tofacitinib 5 mg orally twice daily for 5 months. One patient developed new patches of alopecia during treatment, so the dosing for that patient was increased to 10 mg/5 mg daily.

Adverse events for participants included headaches, upper respiratory infections, and “mild, transient increases in transaminases,” wrote Dr. Lieu and her collaborators. No serious adverse events were reported.

Previous work at Yale had shown that tofacitinib reversed alopecia universalis in a patient who received the medication for plaque psoriasis, and that topical treatment with ruxolitinib, another janus kinase inhibitor, was effective in treating alopecia universalis.

Study limitations included the small sample size and the relatively short duration of follow-up, an important consideration because relapse has been observed after tofacitinib treatment in AA. Still, “Tofacitinib is a promising therapy for the treatment of severe AA in adolescents,” wrote Ms. Liu and her colleagues, recommending randomized clinical trials for further exploration of efficacy and safety in the pediatric population.

[email protected]

On Twitter @karioakes

MINNEAPOLIS – The first study to evaluate tofacitinib’s effectiveness at treating severe alopecia areata in the pediatric population found that the janus kinase inhibitor was effective for more than half of the patients, and well tolerated by all.

Of a case series of 13 pediatric patients who had alopecia areata (AA) and were treated with tofacitinib, 9 (68%) experienced “clinically significant” regrowth of hair, with mean improvement in the Severity of Alopecia Tool (SALT) score of 88% for these responders. The nonresponding group, all of whom had alopecia universalis or totalis, saw essentially no response, with a 1% reduction in SALT score.

Lucy Y. Liu, a medical student at Yale University, New Haven, Conn., presented the findings at the annual meeting of the Society for Pediatric Dermatology.

Ms. Liu and her coinvestigators reported that all of the patients had severe AA by SALT scoring, with an overall mean pretreatment SALT score of 74. Eight of the patients (62%) had alopecia universalis, and two (15%) had alopecia totalis.

The patients ranged in age from 12 to 17 years, with a median age of 15. All but three were male, and patients were an average 9 years old at onset of AA. For patients with alopecia totalis or universalis, the duration of the current episode was a median 1.75 years.

Five patients (38%) had atopic dermatitis, while 1 (8%) had thyroid disease. Three patients (23%) had family members with AA; all but one patient, however, had a family history of autoimmune disease of some sort.

Patients were given tofacitinib 5 mg orally twice daily for 5 months. One patient developed new patches of alopecia during treatment, so the dosing for that patient was increased to 10 mg/5 mg daily.

Adverse events for participants included headaches, upper respiratory infections, and “mild, transient increases in transaminases,” wrote Dr. Lieu and her collaborators. No serious adverse events were reported.

Previous work at Yale had shown that tofacitinib reversed alopecia universalis in a patient who received the medication for plaque psoriasis, and that topical treatment with ruxolitinib, another janus kinase inhibitor, was effective in treating alopecia universalis.

Study limitations included the small sample size and the relatively short duration of follow-up, an important consideration because relapse has been observed after tofacitinib treatment in AA. Still, “Tofacitinib is a promising therapy for the treatment of severe AA in adolescents,” wrote Ms. Liu and her colleagues, recommending randomized clinical trials for further exploration of efficacy and safety in the pediatric population.

[email protected]

On Twitter @karioakes

MINNEAPOLIS – The first study to evaluate tofacitinib’s effectiveness at treating severe alopecia areata in the pediatric population found that the janus kinase inhibitor was effective for more than half of the patients, and well tolerated by all.

Of a case series of 13 pediatric patients who had alopecia areata (AA) and were treated with tofacitinib, 9 (68%) experienced “clinically significant” regrowth of hair, with mean improvement in the Severity of Alopecia Tool (SALT) score of 88% for these responders. The nonresponding group, all of whom had alopecia universalis or totalis, saw essentially no response, with a 1% reduction in SALT score.

Lucy Y. Liu, a medical student at Yale University, New Haven, Conn., presented the findings at the annual meeting of the Society for Pediatric Dermatology.

Ms. Liu and her coinvestigators reported that all of the patients had severe AA by SALT scoring, with an overall mean pretreatment SALT score of 74. Eight of the patients (62%) had alopecia universalis, and two (15%) had alopecia totalis.

The patients ranged in age from 12 to 17 years, with a median age of 15. All but three were male, and patients were an average 9 years old at onset of AA. For patients with alopecia totalis or universalis, the duration of the current episode was a median 1.75 years.

Five patients (38%) had atopic dermatitis, while 1 (8%) had thyroid disease. Three patients (23%) had family members with AA; all but one patient, however, had a family history of autoimmune disease of some sort.

Patients were given tofacitinib 5 mg orally twice daily for 5 months. One patient developed new patches of alopecia during treatment, so the dosing for that patient was increased to 10 mg/5 mg daily.

Adverse events for participants included headaches, upper respiratory infections, and “mild, transient increases in transaminases,” wrote Dr. Lieu and her collaborators. No serious adverse events were reported.

Previous work at Yale had shown that tofacitinib reversed alopecia universalis in a patient who received the medication for plaque psoriasis, and that topical treatment with ruxolitinib, another janus kinase inhibitor, was effective in treating alopecia universalis.

Study limitations included the small sample size and the relatively short duration of follow-up, an important consideration because relapse has been observed after tofacitinib treatment in AA. Still, “Tofacitinib is a promising therapy for the treatment of severe AA in adolescents,” wrote Ms. Liu and her colleagues, recommending randomized clinical trials for further exploration of efficacy and safety in the pediatric population.

[email protected]

On Twitter @karioakes

The National Institute of Allergy and Infectious Diseases (NIAID) has initiated a phase I clinical trial of an investigational vaccine designed to protect against yellow fever virus.

According to an NIAID statement, the study will evaluate whether an experimental vaccine developed by the pharmaceutical manufacturer Bavarian Nordic is “safe, tolerable and has the potential to prevent yellow fever virus infection.”

Courtesy Wikimedia Commons/Muhammad Mahdi Karim/Creative Commons License

Bavarian Nordic’s experimental yellow fever vaccine, called MVA-BN-YF, is based on the company’s proprietary MVA-BN platform, which uses an attenuated version of the Modified Vaccinia Ankara (MVA) virus as a vaccine vector to carry yellow fever virus genes into the body. Bavarian Nordic says that more than 7,600 people, including 1,000 who are immunocompromised, have been safely vaccinated with MVA-BN–based vaccines.

The NIAID statement noted that prior studies have suggested that combining MVA-BN with ISA 720, an experimental immune-boosting adjuvant, induces a strong immune response after a single dose of vaccine. One goal of the study will be to assess whether two doses of unadjuvanted vaccine or a single dose of ISA 720 adjuvanted vaccine could provide protection against yellow fever.

NIAID said the placebo-controlled, double-blinded clinical trial will enroll 90 healthy men and women aged 18-45 years who have never been infected with a flavivirus. Participants will be divided into six groups: One will receive the currently licensed yellow fever vaccine (15 participants) and five groups (15 participants each) will receive the investigational Bavarian Nordic vaccine, either with or without an adjuvant. The investigational vaccine will be administered intramuscularly while the licensed yellow fever vaccine will be administered subcutaneously. Trial participants will receive one or two doses of vaccine or placebo, separated by a month.

According to NIAID’s statement, the multisite trial will be conducted by NIAID-funded Vaccine and Treatment Evaluation Units at the University of Iowa, Iowa City, and Saint Louis (Mo.) University. The Emory Vaccine Center in Decatur, Ga., will assist in evaluating data.

Yellow fever infection usually causes fever, back pain, headache, nausea, vomiting, fatigue, and weakness, but roughly 15% of infected patients develop severe disease manifested as jaundice, hemorrhage, and shock, resulting in potentially fatal kidney, liver, or heart conditions.

The current yellow fever vaccine can produce severe adverse complications, such as neurologic side effects, multiple organ system dysfunction and death, and thus cannot be given to infants, the elderly, pregnant women, and those with compromised immune systems. More than 105 million people in Africa have been vaccinated against yellow fever since 2006, according to the World Health Organization (WHO), but a new outbreak of the disease has caused an estimated 84,000-170,000 severe illnesses and 29,000 to 60,000 deaths in 2013.

For more details about the trial, visit the National Institutes of Health Clinical Trials website.

[email protected]

On Twitter @richpizzi

The National Institute of Allergy and Infectious Diseases (NIAID) has initiated a phase I clinical trial of an investigational vaccine designed to protect against yellow fever virus.

According to an NIAID statement, the study will evaluate whether an experimental vaccine developed by the pharmaceutical manufacturer Bavarian Nordic is “safe, tolerable and has the potential to prevent yellow fever virus infection.”

Courtesy Wikimedia Commons/Muhammad Mahdi Karim/Creative Commons License

Bavarian Nordic’s experimental yellow fever vaccine, called MVA-BN-YF, is based on the company’s proprietary MVA-BN platform, which uses an attenuated version of the Modified Vaccinia Ankara (MVA) virus as a vaccine vector to carry yellow fever virus genes into the body. Bavarian Nordic says that more than 7,600 people, including 1,000 who are immunocompromised, have been safely vaccinated with MVA-BN–based vaccines.

The NIAID statement noted that prior studies have suggested that combining MVA-BN with ISA 720, an experimental immune-boosting adjuvant, induces a strong immune response after a single dose of vaccine. One goal of the study will be to assess whether two doses of unadjuvanted vaccine or a single dose of ISA 720 adjuvanted vaccine could provide protection against yellow fever.

NIAID said the placebo-controlled, double-blinded clinical trial will enroll 90 healthy men and women aged 18-45 years who have never been infected with a flavivirus. Participants will be divided into six groups: One will receive the currently licensed yellow fever vaccine (15 participants) and five groups (15 participants each) will receive the investigational Bavarian Nordic vaccine, either with or without an adjuvant. The investigational vaccine will be administered intramuscularly while the licensed yellow fever vaccine will be administered subcutaneously. Trial participants will receive one or two doses of vaccine or placebo, separated by a month.

According to NIAID’s statement, the multisite trial will be conducted by NIAID-funded Vaccine and Treatment Evaluation Units at the University of Iowa, Iowa City, and Saint Louis (Mo.) University. The Emory Vaccine Center in Decatur, Ga., will assist in evaluating data.

Yellow fever infection usually causes fever, back pain, headache, nausea, vomiting, fatigue, and weakness, but roughly 15% of infected patients develop severe disease manifested as jaundice, hemorrhage, and shock, resulting in potentially fatal kidney, liver, or heart conditions.

The current yellow fever vaccine can produce severe adverse complications, such as neurologic side effects, multiple organ system dysfunction and death, and thus cannot be given to infants, the elderly, pregnant women, and those with compromised immune systems. More than 105 million people in Africa have been vaccinated against yellow fever since 2006, according to the World Health Organization (WHO), but a new outbreak of the disease has caused an estimated 84,000-170,000 severe illnesses and 29,000 to 60,000 deaths in 2013.

For more details about the trial, visit the National Institutes of Health Clinical Trials website.

[email protected]

On Twitter @richpizzi

The National Institute of Allergy and Infectious Diseases (NIAID) has initiated a phase I clinical trial of an investigational vaccine designed to protect against yellow fever virus.

According to an NIAID statement, the study will evaluate whether an experimental vaccine developed by the pharmaceutical manufacturer Bavarian Nordic is “safe, tolerable and has the potential to prevent yellow fever virus infection.”

Courtesy Wikimedia Commons/Muhammad Mahdi Karim/Creative Commons License

Bavarian Nordic’s experimental yellow fever vaccine, called MVA-BN-YF, is based on the company’s proprietary MVA-BN platform, which uses an attenuated version of the Modified Vaccinia Ankara (MVA) virus as a vaccine vector to carry yellow fever virus genes into the body. Bavarian Nordic says that more than 7,600 people, including 1,000 who are immunocompromised, have been safely vaccinated with MVA-BN–based vaccines.

The NIAID statement noted that prior studies have suggested that combining MVA-BN with ISA 720, an experimental immune-boosting adjuvant, induces a strong immune response after a single dose of vaccine. One goal of the study will be to assess whether two doses of unadjuvanted vaccine or a single dose of ISA 720 adjuvanted vaccine could provide protection against yellow fever.

NIAID said the placebo-controlled, double-blinded clinical trial will enroll 90 healthy men and women aged 18-45 years who have never been infected with a flavivirus. Participants will be divided into six groups: One will receive the currently licensed yellow fever vaccine (15 participants) and five groups (15 participants each) will receive the investigational Bavarian Nordic vaccine, either with or without an adjuvant. The investigational vaccine will be administered intramuscularly while the licensed yellow fever vaccine will be administered subcutaneously. Trial participants will receive one or two doses of vaccine or placebo, separated by a month.

According to NIAID’s statement, the multisite trial will be conducted by NIAID-funded Vaccine and Treatment Evaluation Units at the University of Iowa, Iowa City, and Saint Louis (Mo.) University. The Emory Vaccine Center in Decatur, Ga., will assist in evaluating data.

Yellow fever infection usually causes fever, back pain, headache, nausea, vomiting, fatigue, and weakness, but roughly 15% of infected patients develop severe disease manifested as jaundice, hemorrhage, and shock, resulting in potentially fatal kidney, liver, or heart conditions.

The current yellow fever vaccine can produce severe adverse complications, such as neurologic side effects, multiple organ system dysfunction and death, and thus cannot be given to infants, the elderly, pregnant women, and those with compromised immune systems. More than 105 million people in Africa have been vaccinated against yellow fever since 2006, according to the World Health Organization (WHO), but a new outbreak of the disease has caused an estimated 84,000-170,000 severe illnesses and 29,000 to 60,000 deaths in 2013.

For more details about the trial, visit the National Institutes of Health Clinical Trials website.

[email protected]

On Twitter @richpizzi