The Observatory

Feb. 23, 2016

Infectious Disease

CDC goes to highest alert over Zika outbreak. The United States Centers for Disease Control and Prevention (CDC) said that the agency’s command center is going to its highest level of alert, a measure reflecting growing concern about the prospect of the Zika virus gaining a foothold in the mainland U.S.

The decision reflects the urgent demand for CDC support. Since the CDC activated the Emergency Operations Center on Jan. 22nd, agency spokesman Tom Skinner says, the clamor “for resources has increased to the extent that we need to go to this level to meet the demand.”

This represents the fourth time that the CDC’s command center has declared a Level 1 alert. The other emergencies were Hurricane Katrina, the H1N1 flu threat in 2009, and the Ebola epidemic in West Africa. During emergencies, the command center is staffed by a shifting cast of experts in fields required for the current emergency. In this case, the agency has called together more than 300 experts in insect-borne viruses, reproductive health, and birth and developmental defects.

So far, 50 cases have been identified in the U.S., with several in Texas, Illinois, California, and Washington, D.C. In early February, Florida Gov. Rick Scott declared a state of emergency in four counties, where health officials have diagnosed nine cases of Zika virus in travelers returning from areas affected by Zika.

The CDC scientists are collaborating with local, national, and international partners to study the virus, track its spread, assess the accuracy of Zika-related data, and exchange information about the pandemic as it evolves. Command center personnel also have the resources to ship diagnostic kits, samples and specimens, and emergency-response personnel to Zika hotspots.

CDC, WHO offer resources on Zika virus. On the heels of the World Health Organization (WHO) declaring the spread of the Zika virus an international emergency on Feb. 1, both WHO and the Centers for Disease Control and Prevention (CDC) have compiled resources and information on the virus for physicians and patients.

Zika is a disease caused by a virus that is acquired through the bite of an infected Aedes species mosquito. The most common symptoms of the disease are fever, rash, joint pain, and conjunctivitis, per the CDC. Symptoms can last anywhere from a few days to a week. A severe reaction that would require hospitalization is at this point uncommon, the CDC states on its website.

The first confirmed case of the virus was in May 2015 in Brazil, and the CDC has issued warnings to travelers to that region, as well as other countries where the virus is present. As of early February, the CDC reported that more than 30 cases had been confirmed in the United States in returning travelers.

According to the Dallas County Health and Human Services, the CDC confirmed on Feb. 2 the first case in the U.S. of the Zika virus being acquired through sexual transmission. “The patient was infected with the virus after having sexual contact with an ill individual who returned from a country where Zika virus is present,” the statement read.

Red Cross asks blood donors to wait 28 days after visiting Zika areas. The American Red Cross appealed to prospective donors who have visited Zika outbreak zones to wait at least 28 days before giving blood, but said the risk of transmitting the virus through blood donations remained “extremely” low in the continental United States.

The “self-deferral” notice for blood donors should apply to those who have visited Mexico, the Caribbean, or Central or South America. The Washington-based nonprofit disaster relief agency also asked that donors who give blood and subsequently develop symptoms consistent with Zika within 14 days of donating to notify the Red Cross so the product can be quarantined.

Cases of the Zika virus have been reported in more than 30 countries and territories. The mosquito-borne illness has been linked to a dangerous birth defect called microcephaly, marked by abnormally small head size, and to a serious autoimmune disorder called
Guillian-Barre syndrome that can cause paralysis.

The most common symptoms of infection are flu-like, such as aches and fever. About 80 percent of people infected show no symptoms whatsoever, says Susan Stramer, a microbiologist for the Red Cross. There is no blood test for the disease.

The travel-related donor self-deferral notice, the first measure of its kind taken by the Red Cross for a mosquito-borne disease, came a day after the American Association of Blood Banks, an accrediting organization, called for action, Stramer said.

CDC issues new safe-sex guidelines around Zika virus. Men exposed to the Zika virus and who have a pregnant partner should use a condom or abstain from sex until the baby is born, the Centers for Disease Control and Prevention (CDC) advised in guidelines aimed at preventing sexual transmission of the virus.

In late January, the CDC advised that any pregnant woman with symptoms of Zika should be tested for the virus. The agency added guidelines for pregnant women who fear they have been exposed to the virus but have no symptoms. Those tests would be serological blood tests, in addition to the ultrasounds recommended in the CDC’s first round of guidance.

“Men who live in or travel to areas of active Zika infections and who have a pregnant sexual partner should use latex condoms correctly, or refrain from sex until the pregnancy has come to term,” CDC Director Thomas Frieden MD, MPH, told CNN’s Sanjay Gupta, “or until a test is available to see if he could possibly infect her.”

While a study showed that Zika only stayed viable in blood and saliva for a week, “we don’t know how long Zika can persist in semen,” Frieden said. “We’re doing those tests now, but it could be weeks to months before we have an answer.”

Frieden added that the risk for developing Zika depends on how long a person was in the area where Zika is present, how many mosquitoes are active in that area, how many mosquito bites they had, and how well they protected themselves.

“We are not issuing guidance on kissing,” Frieden said. “We take all reports seriously, but we need more information including the methodology of any study. The bottom line is that Zika is primarily a mosquito-borne disease.”

Health officials had previously reported isolated instances of the virus being passed via blood transfusions and sexual contact. The virus has spread to at least 29 countries.

As many as three to four million people across the Americas will be infected with the virus in the next year, WHO has estimated.

Lyme disease just got nastier. Until now, scientists thought that the tick-borne illness was caused by only one species of bacteria, called Borrelia burgdorferi. But scientists from the Centers for Disease Control and Prevention (CDC) and the Mayo Clinic have discovered that a second, related species of bacteria, Borrelia mayonii, can infect people who have been bitten by the black-legged deer tick.

The new bacteria cause similar symptoms in the early stage of infection, such as fever, headache, rash, and neck pain. Arthritis can set in weeks later. But unlike B. burgdorferi, B. mayonii can inflict nausea and vomiting as well. It also may cause a diffuse rash, different from the telltale “bull’s-eye” rash doctors peg to the original Lyme infection.

Each year, about 300,000 people in the United States are diagnosed with Lyme disease, according to the CDC. Most cases are concentrated in the Northeast and upper Midwest. The new Lyme-linked species so far appears to be a risk to tick-bite sufferers only in the upper Midwest, including Minnesota and Wisconsin, the scientists report.

The CDC has initiated a project to detect and characterize species of bacteria in specimens from patients suspected of tick-borne illnesses. Over the next several years, scientists aim to test as many as 30,000 patient samples to gain more information.

The CDC recommends hikers reduce their risk of tick-borne infections by avoiding woody and brushy areas with high grass, walking in the center of trails, using insect repellents with DEET or permethrin, and wearing protective clothing.

Cancer

NIH researchers identify striking genomic signature shared by five types of cancer. National Institutes of Health (NIH) researchers have identified a striking signature in tumor DNA that occurs in five different types of cancer. They also found evidence that this methylation signature may be present in many more types of cancer.

The specific signature results from a chemical modification of DNA called methylation, which can control the expression of genes like a dimmer on a light switch. Higher amounts of DNA methylation (hypermethylation), like that found by the researchers in some tumor DNA, decrease a gene’s activity. Based on this advance, the researchers hope to spur development of a blood test that can be used to diagnose a variety of cancers at early stages, when treatments can be most effective. The study appeared Feb. 5, 2016, in The Journal of Molecular Diagnostics.

In this new study, researchers developed a series of steps that uncovered telltale methylation marks in colon, lung, breast, stomach, and endometrial cancers. They showed that all the tumor types and subtypes consistently produced the same methylation mark around ZNF154.

The NIH Intramural Sequencing Center sequenced the tumor DNA that had been amplified using polymerase chain reaction (PCR). Researchers then analyzed the results, finding elevated levels of methylation at ZNF154 across the different tumor types.

The researchers do not yet understand the connection between tumors and elevated DNA methylation. It may represent derailment of normal processes in the cell, or it may have something to do with the fact that tumors consume a lot of energy and circumvent the cellular processes that keep growth in check. The scientists also don’t know exactly what the gene ZNF154 does.

Genetics/Genomics

Researchers discover 10 new lupus genes in Asian population study. An international coalition of researchers led by Swapan Nath, PhD, has identified 10 new genes associated with the autoimmune disease lupus. The findings were published in Nature Genetics.

The researchers analyzed more than 17,000 human DNA samples collected from blood gathered from volunteers in South Korea, China, Malaysia, and Japan. Of those samples, nearly 4,500 had confirmed cases of lupus, while the rest served as healthy controls.

From analysis of those samples, the researchers identified 10 distinct DNA sequence variants linked to lupus, a debilitating chronic autoimmune disease where the body’s immune system becomes unbalanced and attacks its own tissues. Lupus can result in damage to many different body systems, including the joints, skin, kidneys, heart, and lungs. More than 16,000 people are diagnosed with lupus in the United States each year, and it affects as many as 1.5 million Americans and five million people worldwide.

Thirty-seven researchers from 23 institutes, hospitals, and universities in the U.S., Malaysia, Korea, China, and Japan took part in Nath’s study.

In the study, one gene in particular, known as GTF2I, showed a high likelihood of being involved in the development of lupus. With GTF21 and the other nine new genes identified, Nath and his colleagues can try to pinpoint where defects occur and whether those mutations contribute to the onset of lupus pathogenesis. Nath says that understanding where and how the defects arise will allow scientists to develop more effective therapies specifically targeting those genes.

New Studies

New marker predicts joint damage in RA. A novel biomarker found in elevated levels in the serum and synovium of patients with early rheumatoid arthritis (RA) could help predict which patients would have worse radiographic damage, Canadian researchers report.

In a univariate analysis, the baseline factors that in combination best predicted erosive progression over five years were age 65 or older, C-reactive protein (CRP) above 8 mg/L, and a level of the new biomarker 14-3-3η of 0.50 ng/mL or higher, according to Gilles Boire, MD, of the University of Sherbrooke in Quebec, and colleagues.

The relative risk of erosive progression with all three of those variables was 5.49 compared with the absence of all three, the researchers reported online in Arthritis Research & Therapy. “14-3-3η-positive status can thus assist primary care providers during referral of patients to rheumatologists, and may help rapid initiation of a targeted pharmacologic intervention,” they said.

As the treat-to-target approach to RA has become widely adopted, it has become clear that current biomarkers are inadequate to help predict which patients are at highest risk and may need intensified treatment, with one study suggesting that conventional variables such as rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP), and CRP account for only 32 percent of variance in prediction of joint damage.

Researchers have therefore been searching for additional markers, and Boire’s group has identified the 14-3-3 family of intracellular proteins, and specifically the η isoform, as potential candidates.

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