Category: Centers for Disease Control and Prevention

The Recovering Americans and the ‘Top Secret’ Ebola Treatment

On By A.P.In Africa, CDC, Centers for Disease Control and Prevention, Ebola, Ebola Consolidation Case Management Center, ebola vaccine, Emory University, Emory University School of Medicine, Kebmodee, Kent Brantly, Liberia, Mapp Biopharmaceuticals, Margaret Chan, Medicine, monoclonal antibody, National Institutes of Health, NIAID, NIH, Samaritan's Purse, Sanjay Gupta, Science, World Health Organization, zMappLeave a comment

Because Kent Brantly is a physician who has watched people die of Ebola, there was an especially chilling prescience to his assessment last week, between labored breaths: “I am going to die.”

His condition was grave. But then on Saturday, we saw images of Brantly’s heroic return to U.S. soil, walking with minimal assistance from an ambulance into an isolation unit at Emory University Hospital.

“One of the doctors called it ‘miraculous,'” Dr. Sanjay Gupta reported from Emory this morning, of Brantly’s turnaround within hours of receiving a treatment delivered from the U.S. National Institutes of Health. “Not a term we scientists like to throw around.”

“The outbreak is moving faster than our efforts to control it,” Dr. Margaret Chan, director of the World Health Organization, said on Friday in a plea for international help containing the virus. “If the situation continues to deteriorate, the consequences can be catastrophic in terms of lost lives, but also severe socioeconomic disruption and a high risk of spread to other countries.”

In that light, and because Ebola is notoriously incurable (and the strain at large its most lethal), it is overwhelming to hear that “Secret Serum Likely Saved Ebola Patients,” as we do this morning from Gupta’s every-20-minute CNN reports. He writes:

Three top secret, experimental vials stored at subzero temperatures were flown into Liberia last week in a last-ditch effort to save two American missionary workers [Dr. Kent Brantly and Nancy Writebol] who had contracted Ebola, according to a source familiar with details of the treatment.

Brantly had been working for the Christian aid organization Samaritan’s Purse as medical director of the Ebola Consolidation Case Management Center in Monrovia, Liberia. The group yesterday confirmed that he received a dose of an experimental serum before leaving the country.

In Gupta’s optimistic assessment, Brantly’s “near complete recovery” began within hours of receiving the treatment that “likely saved his life.” Writebol is also reportedly improved since receiving the treatment, known as zMapp. But to say that it was a secret implies a frigid American exceptionalism; that the people of West Africa are dying in droves while a classified cure lies in wait.

The “top-secret serum” is a monoclonal antibody. Administration of monoclonal antibodies is an increasingly common but time-tested approach to eradicating interlopers in the human body. In a basic monoclonal antibody paradigm, scientists infect animals (in this case mice) with a disease, the mice mount an immune response (antibodies to fight the disease), and then the scientists harvest those antibodies and give them to infected humans. It’s an especially promising area in cancer treatment.

In this case, the proprietary blend of three monoclonal antibodies known as zMapp had never been tested in humans. It had previously been tested in eight monkeys with Ebola who survived—though all received treatment within 48 hours of being infected. A monkey treated outside of that exposure window did not survive. That means very little is known about the safety and effectiveness of this treatment—so little that outside of extreme circumstances like this, it would not be legal to use. Gupta speculates that the FDA may have allowed it under the compassionate use exemption.

A small 2012 study of monoclonal antibody therapy against Ebola found that it was only effective when administered before or just after exposure to the virus. A 2013 study found that rhesus macaques given an antibody mix called MB-003 within the 48-hour window had a 43 percent chance of surviving—as opposed to their untreated counterparts, whose survival rate was zero.

This Ebola outbreak is the largest in the history of the disease, in terms of both cases and deaths, 729 887 known so far. As Chan warned in her call for urgent international action, the outbreak is geographically the largest, already in four countries with fluid population movement across porous borders and a demonstrated ability to spread by air travel. The outbreak will be stopped by strategic quarantines and preventive education, primarily proper handling of corpses. More than 60 aid workers have become infected, but many more will be needed to stem the tide.

Dr. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Disease (NIAID), is encouraged by the antibody treatment.

“Obviously there are plans and enthusiasm to expand this,” Fauci told me. “The limiting factor is the extraordinary paucity of treatment regimens.” Right now the total amount available, to Fauci’s knowledge, is three treatment courses (in addition to what was given to Brantly and Writebol).

NIAID did some of the original research that led to the development, but this is owned by Mapp Biopharmaceuticals. “They are certainly trying to scale up,” Fauci said, “but I’ve heard that their capability is such that it’s going to be months before they have a substantial number of doses, and even then they’re going to be limited.”

“We’re hearing that the administration of this cocktail of antibodies improved both Dr. Brantly and Ms. Writebol, but you know, we don’t know that,” Fauci said, noting the sample size (two) of this small, ad hoc study. Proving effectiveness would require a much larger group of patients being compared to an untreated group. “And we don’t know that they weren’t getting better anyway.”

Thanks to Kebmodee for bringing this to the attention of the It’s Interesting community.

http://www.theatlantic.com/health/archive/2014/08/the-secret-ebola-treatment/375525/

New study shows that anger outbursts acutely raise risk of heart attack and stroke

On By A.P.In acute coronary syndrome, American Heart Association, anger, anger outburst, blood pressure, cardiovascular disease, Centers for Disease Control and Prevention, diabetes, European Heart Journal, Harvard, Harvard Medical School, Harvard University, Health, Heart Attack, heart attack, high blood pressure, high cholesterol, hypercholesterolemia, Hypertension, hypertension, infective endocarditis, Mariell Jessup, Medicine, Murray A. Mittleman, myocardial infarction, Penn Heart and Vascular Center, Science, smoking, stress, stroke, sympathetic nervous system, University of PennsylvaniaLeave a comment

Getting really angry might be more dangerous than you think.

A new study found people who experienced severe anger outbursts were more at risk for cardiovascular events in the two hours following the outbursts compared to those who remained calm.

“The relative risk was similar for people who had known pre-existing heart disease and those who didn’t,” says Dr. Murray A. Mittleman, senior study author and an associate professor of medicine at Harvard Medical School.

The study was designed so that each patient was compared to his or her own baseline risk. “A person with pre-existing heart disease or cardiovascular disease, the absolute risk they are incurring is much greater than (that of) a person without cardiovascular disease or risk factors,” Mittleman says.
“If we look at somebody at higher risk for having cardiovascular events, and they get angry multiple times a day, this can lead to 650 extra heart attacks per year out of 10, 000 a year,” he says. “When we look at a person who is relatively low risk, but if they do have these episodes of anger fairly frequently, we estimate there would be about 150 extra heart attacks out of 10,000 a year.”

Smoking, high cholesterol, high blood pressure, being overweight and having diabetes are all risk factors for cardiovascular disease. An estimated 17 million people worldwide die of cardiovascular diseases, particularly heart attacks and strokes, each year, according to the Centers for Disease Control and Prevention.

The study published Monday in the European Heart Journal was a data analysis looking at nine studies where anger and cardiovascular events were self-reported over nearly two decades. The study found a 4.74 times higher risk of MI (myocardial infarction, or heart attack) or ACS (acute coronary syndrome, where the heart muscle doesn’t get enough oxygen-rich blood) following outbursts of anger.

“Anger causes our heart rate to increase through the sympathetic nervous system and causes our stress hormones to become elevated (the fight or flight mechanism),” says Dr. Mariell Jessup, president of the American Heart Association and medical director of the Penn Heart and Vascular Center at the University of Pennsylvania. “We breathe faster, all of which may trigger undesirable reactions in our blood pressure or in our arteries.”

This disruption may mean the heart or the brain doesn’t get the blood and oxygen they need resulting in a heart attack or a stroke, she says.

Researchers suggest more needs to be done to come up with effective interventions to prevent cardiovascular events triggered by anger outbursts. The American Heart Association suggests regular physical activity, finding a way to relax or talking with friends to help reduce stress and anger.

Mittleman suggests the best way to lower your risk for a heart attack or stroke during an angry outburst is to lower your overall baseline level of risk – exercise, eat healthy and don’t smoke – and then find ways to cope with stress and anger.

Angry outbursts may raise heart attack, stroke risk

University of Iowa researchers uncover mechanism of infective endocarditis

On By A.P.In 11th International Conference on Wirtschaftsinformatik, Alexander Horswill, Bacteria, Carver College of Medicine, CDC, Centers for Disease Control and Prevention, Christopher Stach, endocarditis, heart, infective endocarditis, Iowa, Iowa City, Joseph Merriman, Laura Breshears, Marnie Peterson, Medicine, microbiology, Patrick Schlievert, Science, Staphylococcus aureus, superantigen, toxic shock syndrome toxin, toxic shock syndrome toxin-1, University of Iowa, University of Iowa Hospitals and Clinics, Wilmara Salgado-PabonLeave a comment

heart infection

University of Iowa researchers have discovered what causes the lethal effects of staphylococcal infective endocarditis – a serious bacterial infection of heart valves that kills approximately 20,000 Americans each year. According to the UI study, the culprits are superantigens — toxins produced in large quantities by Staphylococcus aureus bacteria — which disrupt the immune system, turning it from friend to foe.

“The function of a superantigen is to ‘mess’ with the immune system,” says Patrick Schlievert, PhD, UI professor and chair of microbiology at the UI Carver College of Medicine. “Our study shows that in endocarditis, a superantigen is over-activating the immune system, and the excessive immune response is actually contributing very significantly to the destructive aspects of the disease, including capillary leakage, low blood pressure, shock, fever, destruction of the heart valves, and strokes that may occur in half of patients.”

Other superantigens include toxic shock syndrome toxin-1, which Schlievert identified in 1981 as the cause of toxic shock syndrome.

Staph bacteria is the most significant cause of serious infectious diseases in the United States, according to the Centers for Disease Control and Prevention (CDC), and infective endocarditis is the most serious complication of staph bloodstream infection. This dangerous condition affects approximately 40,000 people annually and has a death rate of about 50 percent. Among patients who survive the infection, approximately half will have a stroke due to the damage from the aggressive infection of the heart valves.

Despite the serious nature of this disease, little progress has been made over the past several decades in treating the deadly condition.

The new study, led Schlievert, and published Aug. 20 in the online open-access journal mBio, suggests that blocking the action of superantigens might provide a new approach for treating infective endocarditis.

“We have high affinity molecules that neutralize superantigens and we have previously shown in experimental animals that we can actually prevent strokes associated with endocarditis in animal models. Likewise, we have shown that we can vaccinate against the superantigens and prevent serious disease in animals,” Schlievert says.

“The idea is that either therapeutics or vaccination might be a strategy to block the harmful effects of the superantigens, which gives us the chance to do something about the most serious complications of staph infections.”

The UI scientists used a strain of methicillin resistant staph aureus (MRSA), which is a common cause of endocarditis in humans, in the study. They also tested versions of the bacteria that are unable to produce superantigens. By comparing the outcomes in the animal model of infection with these various bacteria, the team proved that the lethal effects of endocarditis and sepsis are caused by the large quantities of the superantigen staphylococcal enterotoxin C (SEC) produced by the staph bacteria.

The study found that SEC contributes to disease both through disruption of the immune system, causing excessive immune response to the infection and low blood pressure, and direct toxicity to the cells lining the heart.

Low blood flow at the infection site appears to be one of the consequences of the superantigen’s action. Increasing blood pressure by replacing fluids reduced the formation of so-called vegetations – plaque-like meshwork made up of cellular factors from the body and bacterial cells — on the heart valves and significantly protected the infected animals from endocarditis. The researchers speculate that increased blood flow may act to wash away the superantigen molecules or to prevent the bacteria from settling and accumulating on the heart valves.

In addition to Schlievert, the research team included Wilmara Salgado-Pabon, PhD, the first author on the study, Laura Breshears, Adam Spaulding, Joseph Merriman, Christopher Stach, Alexander Horswill, and Marnie Peterson.

The research was funded in part by grants from the National Institutes of Health (AI74283, AI57153, AI83211, and AI73366).

http://www.infectioncontroltoday.com/news/2013/08/bacterial-toxins-cause-deadly-heart-disease.aspx