The Observatory

March 23, 2016

Infectious Disease

New CDC laboratory test for Zika virus authorized for emergency use by FDA. In response to a request from the Centers for Disease Control and Prevention (CDC), the United States Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for a diagnostic tool for Zika virus that will be distributed to qualified laboratories and, in the United States, those that are certified to perform high-complexity tests.

The test, called the CDC Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA), is intended for use in detecting antibodies that the body makes to fight a Zika virus infection. These antibodies (in this case, immunoglobulin M, or IgM) appear in the blood of a person infected with Zika virus beginning four to five days after the start of illness and last for about 12 weeks. The test is intended to be used on blood samples from people with a history of symptoms associated with Zika and/or people who have recently traveled to an area during a time of active Zika transmission.

The FDA can use the EUA to permit use, based on scientific data, of certain medical products in certain circumstances, including when there is a determination by the Secretary of Health and Human Services that there is significant potential for a public health emergency that has significant potential to affect national security or the health and security of U.S. citizens. As there are no commercially available diagnostic tests cleared or approved by the FDA for the detection of Zika virus infection, it was determined that an EUA is crucial to ensure timely access to a diagnostic tool. The CDC’s Zika MAC-ELISA is the first diagnostic test authorized for use in the U.S. for the detection of Zika virus during this situation in which there has been a determination that there is a significant potential for a public health emergency that has a significant potential to affect national security or the health and security of citizens living abroad and that involves Zika virus.

Results of Zika MAC-ELISA tests require careful interpretation. A positive test result indicates that a person was likely infected recently with the Zika virus. However, the test can give an incorrect positive. These false-positive results can occur when someone has been infected with another closely related virus (such as dengue virus). When positive or inconclusive results occur, additional testing (plaque reduction neutralization test) to confirm the presence of antibodies to Zika virus will be performed by the CDC or a CDC-authorized laboratory.

Moreover, a negative test result does not necessarily mean that a person has not been infected with Zika virus. If a sample is collected just after a person becomes ill, there may not be enough antibodies for the test to measure, resulting in a false negative. Similarly, if the sample is collected more than 12 weeks after illness, it is possible that the body has successfully fought the virus and antibody levels have dropped below the detectable limit.

As with any test, it is important that healthcare providers consult with their patients about test results and the best approach to monitoring their health.

The CDC began distributing the test last month to qualified laboratories in the Laboratory Response Network, an integrated network of domestic and international laboratories that can respond to public health emergencies. The test will not be available in U.S. hospitals or other primary care settings. Public health officials anticipate that distribution of the tests will improve laboratory testing capacity for Zika virus in the U.S.

Zika virus associated with meningoencephalitis. An 81-year-old man was admitted to the intensive care unit 10 days after he had been on a four-week cruise in the area of New Caledonia, Vanuatu, the Solomon Islands, and New Zealand; he was reported to have been in perfect health during that time.

On medical examination, he was febrile and comatose with hemiplegia of the left side, paresis of the right upper limb, a normal response to tendon reflexes, and a Babinski sign on the left side. The patient’s trachea was intubated and mechanical ventilation begun; a transient rash was observed within the next 48 hours. Magnetic resonance imaging (MRI) of the brain was suggestive of meningoencephalitis.

Computed tomographic angiography revealed an irregular narrowing of the right callosomarginal artery.

A lumbar puncture was performed on day 1, and findings on analysis of cerebrospinal fluid (CSF) were suggestive of meningitis: the leukocyte count was 41 per cubic millimeter (with 98% polymorphonuclear leukocytes), the protein level was 76 mg per deciliter, and the ratio of CSF to blood glucose was 0.75. The patient was initially treated with amoxicillin, cefotaxime, gentamicin, and acyclovir, but these antimicrobial agents were stopped on day 5. Investigations in both CSF and blood for other infections were unrevealing except for a positive result for ZIKV on reverse-transcriptase–polymerase-chain-reaction assay of the CSF. ZIKV was grown in culture from the CSF on a Vero cell line.

These findings all support the diagnosis of ZIKV-associated meningoencephalitis.

New Studies

Common blood test could predict risk of second stroke. A new discovery about ischemic stroke may allow doctors to predict a patient’s risk of having a second stroke using a commonly performed blood test and their genetic profile.

The researchers have linked high levels of C-reactive protein, an enzyme found in the blood, with higher risk for recurrent ischemic stroke. C-reactive protein (CRP) is produced in the liver in response to inflammation, and it is already checked to measure risk of developing coronary artery disease. The new research suggests it could be a useful tool for ischemic stroke patients as well.

Researchers set out to determine how genes affect the levels of biomarkers such as CRP in the blood. Not only did they find that elevated CRP levels suggest increased stroke risk, but they identified gene variations that drive that risk.

Researchers envision a day when doctors might focus on CRP levels and a patient’s genetic makeup to determine the overall risk for a second stroke. But CRP levels alone could be a useful tool in assessing risk after the initial stroke.


Low vitamin D predicts aggressive prostate cancer. A new study provides a major link between low levels of vitamin D and aggressive prostate cancer. Northwestern Medicine research showed that deficient vitamin D blood levels in men can predict aggressive prostate cancer identified at the time of surgery. The finding is important because it can offer guidance to men and their doctors who may be considering active surveillance, in which they monitor the cancer rather than remove the prostate.

Previous studies showing an association between vitamin D levels and aggressive prostate cancer were based on blood drawn well before treatment. The new study provides a more direct correlation because it measured D levels within a couple of months before the tumor was visually identified as aggressive during surgery to remove the prostate.


Alcohol exposure during pregnancy affects multiple generations. When a mother drinks alcohol during pregnancy, even a small dose, she can increase the chances that the next three generations may develop alcoholism, according to a new study.

A research team led by Nicole Cameron, PhD, was the first to investigate the effects of alcohol consumption during pregnancy on alcohol-related behavior (consumption and sensitivity to the effect of alcohol) on generations that were not directly exposed to alcohol in the uterus during the pregnancy.

Pregnant rats received the equivalent of one glass of wine, four days in a row, at gestational days 17-20, which is the equivalent of the second trimester in humans. Juvenile male and female offspring were then tested for water or alcohol consumption. Adolescent males were tested for sensitivity to alcohol by injecting them with a high-alcohol dose, which made them unresponsive, and measuring the time it took them to recover their senses. The results suggest that if a mother drinks during pregnancy, even just a little, she increases the risk that her progeny will become alcoholic.

Drugs of Abuse

Overdose deaths from common sedatives have surged, new study finds. Headlines about America’s worsening drug epidemic have focused on deaths from opioids—heroin and prescription painkillers such as OxyContin. But overdose deaths have also soared among the millions of Americans using benzodiazepine drugs, a class of sedatives that includes Xanax, Valium, and Klonopin, according to a study led by researchers at Albert Einstein College of Medicine, Montefiore Health System and the Perelman School of Medicine at University of Pennsylvania.

“We found that the death rate from overdoses involving benzodiazepines, also known as ‘benzos,’ has increased more than four-fold since 1996—a public health problem that has gone under the radar,” says lead author Marcus Bachhuber, MD, MS. Overdoses from benzodiazepines have increased at a much faster rate than prescriptions for the drugs, indicating that people have been taking them in a riskier way over time.”

In 2013, benzodiazepine overdoses accounted for 31 percent of the nearly 23,000 deaths from prescription drug overdoses in the U.S. But little was known about the national trends in benzodiazepine prescribing or in fatalities from the drug.

The researchers’ analysis revealed that the number of adults purchasing a benzodiazepine prescription increased by 67 percent over the 18-year period, from 8.1 million prescriptions in 1996 to 13.5 million in 2013. For those obtaining benzodiazepine prescriptions, the average quantity filled during the year more than doubled between 1996 and 2013. Most crucially, the overdose death rate over the 18-year period increased from 0.58 deaths per 100,000 adults in 1996 to 3.14 deaths per 100,000 adults in 2013, a more than four-fold increase. Overall, the rate of overdose deaths from benzodiazepines has leveled off since 2010. But for a few groups—adults aged 65 and over, and blacks and Hispanics—the rate of overdose deaths after 2010 continued to rise.

Alzheimer’s Disease

Researchers identify virus and two types of bacteria as major causes of Alzheimer’s. A worldwide team of senior scientists and clinicians have come together to produce an editorial which indicates that certain microbes—a specific virus and two specific types of bacteria—are major causes of Alzheimer’s Disease (AD).

This major call for action is based on substantial published evidence into AD. The team’s landmark editorial summarizes the abundant data implicating these microbes, but until now this work has been largely ignored or dismissed as controversial. Therefore, proposals for the funding of clinical trials have been refused, despite the fact that over 400 unsuccessful clinical trials for AD based on other concepts were carried out over a recent 10-year period.

“We are saying there is incontrovertible evidence that Alzheimer’s Disease has a dormant microbial component, and that this can be woken up by iron dysregulation. Removing this iron will slow down or prevent cognitive degeneration. We can’t keep ignoring all of the evidence,” Professor Douglas Kell says.

Professor Resia Pretorius, who also worked on the editorial, says “The microbial presence in blood may also play a fundamental role as causative agent of systemic inflammation, which is a characteristic of Alzheimer’s disease—particularly, the bacterial cell wall component and endotoxin, lipopolysaccharide. Furthermore, there is ample evidence that this can cause neuroinflammation and amyloid-ß plaque formation.”

Swedish study finds potential proteomic biomarkers for Alzheimer’s in cerebrospinal fluid. A mass spectrometry-based analysis of cerebrospinal fluid in Alzheimer’s disease (AD) patients has yielded a handful of potential biomarkers for the disease.

The researchers used label-free shotgun mass spectrometry to look at proteins in the cerebrospinal fluid of 10 AD patients and 10 healthy controls. They also performed protein depletion of high-abundance proteins to improve detection and quantification of low-abundance proteins.

The authors found eight proteins that were differentially expressed between the two study groups. “ApoM, LRG, FBLN3, and PTPRZ have functions related to cell adhesion, migration, and morphology,” and may also be associated with other aging-associated diseases like cancer and diabetes, they wrote. C1QB, C1QC, complement C1S, and SEZ6 may be implicated in synapse development.

“Cerebrospinal fluid is a proximal fluid in direct contact with the brain interstitial fluid that potentially reflects biochemical changes related to [the] central nervous system, making it a promising source of biomarkers in neurological disorders such as AD,” they added. While Alzheimer’s disease is associated with several proteomic markers, especially the protein tau and beta-amyloid peptides, those have limited value for monitoring disease progression.

In their paper, the authors also pointed out other factors that might have influenced results. In addition to the small study size, they noted that there was a slight age difference between the two groups, where the controls were, on average, nine years older than participants in the Alzheimer’s group; protein levels in cerebrospinal fluid are thought to change with age. The lower protein levels could also be the effect of protein depletion.