DiversityNursing Blog

By Meera Senthilingam

"It only takes one virus to get through for a person to be infected," explained Dr. John Mascola. This is true of any viral infection, but in this instance, Mascola is referring to HIV and his ongoing efforts to develop a vaccine against the virus. "It's been so difficult to make an HIV/AIDS vaccine."

Those were the words of many working in HIV vaccine development until the results of a 2009 trial in Thailand surprised everyone. "The field is energized," said Mascola, director of the Vaccine Research Center at the U.S. National Institute of Allergy and Infectious Diseases, describing the change in atmosphere in the vaccine community.

The trial included over 16,000 volunteers and was the largest clinical trial ever conducted for a vaccine against HIV. It was also the first to show any protection at all against infection.

Two previously developed vaccines, known as ALVAC-HIV and AIDSVAX, were used in combination, with the first priming an immune response against HIV and the second used as a booster once the immunity waned. The duo reduced the risk of contracting HIV by 31.2% -- a modest reduction, but it was a start.

To date, only four vaccines have made it as far as testing for efficacy to identify their levels of protection against HIV. Only this one showed any protection.

"That trial was pivotal," Mascola said. "Prior to that, it wasn't known whether a vaccine could be possible."

In recent years, there have been parallel findings of an equally pivotal nature in the field of HIV prevention, including the discovery that people regularly taking their antiretroviral treatment reduce their chances of spreading HIV by 96% and that men who are circumcised reduce their risk of becoming infected heterosexually by approximately 60%.

Both improved access to antiretrovirals and campaigns to increase male circumcision in high-risk populations have taken place since the discoveries, and although numbers of new infections are falling, they're not falling fast enough.

In 2013, there were 35 million people estimated to be living with HIV globally. There were still 2.1 million new infections in 2013, and for every person who began treatment for HIV last year, 1.3 people were newly infected with the lifelong virus, according to UNAIDS. A vaccine remains essential to control the epidemic.

A complex beast

Scientists like Mascola have dedicated their careers to finding a vaccine, and their road has been tough due to the inherently complicated nature of the virus, its aptitude for mutating and changing constantly to evade immune attack, and its ability attack the very immune cells that should block it.

There are nine subtypes of HIV circulating in different populations around the world, according to the World Health Organization, and once inside the body, the virus can change continuously.

"Within an individual, you have millions of variants," explained Dr. Wayne Koff, chief scientific officer for the International AIDS Vaccine Alliance.

HIV invades the body by attaching to, and killing, CD4 cells in the immune system. These cells are needed to send signals for other cells to generate antibodies against viruses such as HIV, and destroying those enables HIV to cause chronic lifelong infections in those affected.

Measles, polio, tetanus, whooping cough -- to name a few -- all have vaccines readily available to protect from their potentially fatal infections. But their biology is seemingly simple in comparison with HIV.

"For the older ones, you identify the virus, either inactivate it or weaken it, and inject it," Koff said. "You trick the body into thinking it is infected with the actual virus, and when you're exposed, you mount a robust immune response."

This is the premise of all vaccines, but the changeability of HIV means the target is constantly changing. A new route is needed, and the true biology of the virus needs to be understood. "In the case of HIV, the old empirical approach isn't going to work," Koff said.

Scientists have identified conserved regions of the virus that don't change as readily, making them prime targets for attack by antibodies. When the success of the Thai trial was studied deep down at the molecular level, the protection seemed to come down to attacking some of these conserved regions. Now it's time to step it up.

In January, the mild success in Thailand will be applied in South Africa, where over 19% of the adult population is living with HIV. The country is second only to bordering Swaziland for having the highest rates of HIV in the world.

"The Thai vaccine was made for strains (of HIV) circulating in Thailand," said Dr. Larry Corey, principal investigator for the HIV Vaccine Trials Network, which is leading the next trial in South Africa. The strain, or subtype, in this case was subtype B. "For South Africa, we've formed a strain with common features to (that) circulating in the population." This region of the world has subtype C.

An additional component, known as an adjuvant, is being added to the mix to stimulate a stronger and hopefully longer-lasting level of immunity. "We know durability in the Thai trial waned," Corey said. If safety trials go well in 2015, larger trials for the protective effect will take place the following year. An ideal vaccine would provide lifelong protection, or at least for a decade, as with the yellow fever vaccine.

A broad attack

The excitement now reinvigorating researchers stems not only from a modestly successful trial but from recent successes in the lab and even from HIV patients themselves.

Some people with HIV naturally produce antibodies that are effective in attacking the HIV virus in many of its forms. Given the great variability of HIV, any means of attacking these conserved parts of the virus will be treasured and the new found gold comes in the form of these antibodies -- known as "broadly neutralizing antibodies." Scientists including Koff set out to identify these antibodies and discover whether they bind to the outer coat of the virus.

The outer envelope, or protein coat, of HIV is what the virus uses to attach to, and enter, cells inside the body. These same coat proteins are what vaccine developers would like our antibodies to attack, in order to prevent the virus from entering our cells. "Broadly neutralizing antibodies" could hold the key because, as their name suggests, they have a broad remit and can attack many subtypes of HIV. "We will have found the Achilles heel of HIV," Koff said.

Out of 1,800 people infected with HIV, Koff and his team found that 10% formed any of these antibodies and just 1% had extremely broad and potent antibodies against HIV. "We called them the elite neutralizers," he said of the latter group. The problem, however, is that these antibodies form too late, when people are already infected. In fact, they usually only form a while after infection. The goal for vaccine teams is to get the body making these ahead of infection.

"We want the antibodies in advance of exposure to HIV," explained Koff. The way to do this goes back to basics: tricking the body into thinking it is infected.

"We can start to make vaccines that are very close mimics of the virus itself," Mascola said.

Teams at his research center have gained detailed insight into the structure of HIV in recent years, particularly the outer coat, where all the action takes place. Synthesizing just the outer coat of a virus in the lab and injecting this into humans as a vaccine could "cause enough of an immune response against a range of types of HIV," Mascola said.

The vaccine would not contain the virus itself, or any of its genetic material, meaning those receiving it have no risk of contracting HIV. But for now, this new area remains just that: new. "We need results in humans," Mascola said.

Rounds of development, safety testing and then formal testing in high-risk populations are needed, but if it goes well, "in 10 years, there could be a first-generation vaccine." If improved protection is seen in South Africa, a first-generation vaccine could be with us sooner.

Making an Impact

When creating vaccines, the desired level of protection is usually 80% to 90%. But the high burden of HIV and potentially beneficial impact of lower levels of protection warrant licensing at a lower percentage.

"Over 50% is worth licensing from a public health perspective," Koff said, meaning that despite less shielding from any contact with the HIV virus, even a partially effective vaccine would save many lives over time.

The next generations will incorporate further advancements, such as inducing neutralizing antibodies, to try to increase protection up to the 80% or 90% desired.

"That's the history of vaccine research; you develop it over time," Corey said. He has worked in the field for over 25 years and has felt the struggle. "I didn't think it would be this long or this hard ... but it's been interesting," he ponders.

But there is light at the end of tunnel. Just.

"There has been no virus controlled without a vaccine," he concluded when explaining why, despite antiretrovirals, circumcision and increased awareness, the need for a one-off intervention like a vaccine remains strong.

"Most people that transmit it don't even know they have it," he said. "To get that epidemic, to say you've controlled it, requires vaccination."

Source: www.cnn.com

Many people have been told, incorrectly, that they're allergic to penicillin, but have not had allergy testing. These people are often given alternative antibiotics prior to surgery to ward off infection. But when antibiotic choices are limited due to resistance, treatment alternatives may be more toxic, more expensive and less effective.

According to two studies presented at the American College of Allergy, Asthma and Immunology (ACAAI) Annual Scientific Meeting, people who believe they have a penicillin allergy would benefit from consultation from an allergist and penicillin allergy skin testing. Once they know if they are allergic, they can be given appropriate -- and not more resistant -- treatment prior to surgery. Of the 384 people in the first study who believed they were allergic to penicillin, 94 percent tested negative for penicillin allergy.

"A large number of people in our study who had a history of penicillin allergy were actually not allergic," said allergist and ACAAI member Thanai Pongdee, MD, lead study author. "They may have had an unfavorable response to penicillin at some point in the past, such as hives or swelling, but they did not demonstrate any evidence of penicillin allergy at the current time. With that in mind, their doctors prescribed different medications prior to surgery."

In the second study, 38 people who believed they were allergic to penicillin were given penicillin skin testing to see if it was possible to help reduce the use of high-cost antibiotics. Of the 38 people tested, all of them tested negative to an allergy for penicillin. Once it was known they weren't allergic to penicillin, the medical center was able to change the medications of 29 of the patients, thereby significantly lowering prescription costs.

"When you are told you have an allergy to something, it's important to be seen and tested by an allergist, who has the specialized training needed for accurate diagnosis and treatment," said allergist James Sublett, ACAAI president-elect. "If you're truly allergic to a medication, your allergist will counsel you on an appropriate substitute."

Source: www.sciencedaily.com

By Sara Cheshire

Can we predict the future of medicine? Although designer babies and a disease-free world may or may not come to pass, you can get a glimpse of the most promising and upcoming medical innovations each year, via the Cleveland Clinic.

The clinic's Top 10 Medical Innovations list, which has been an annual undertaking since 2007, contains treatments and technologies that are expected to significantly change patient care and save lives.

To be considered, each innovation must have a good chance of being available to the public in the upcoming year, says Dr. Michael Roizen, chief wellness officer at the Cleveland Clinic and chairman of the committee that decides the list. The committee must also expect it to have a significant impact on a large part of the population.

The process starts with a panel of Cleveland Clinic physicians and scientists who submit their ideas. These suggestions, which Roizen said totaled about 700 for the 2015 list, are then narrowed down and voted on by 40 physicians in a variety of health fields.

Here's what they selected for 2015:

1. Mobile stroke unit

Videoconferencing has made its way into ambulances, specifically for treating stroke victims on the go. Hospital stroke neurologists can interpret symptoms via a broadband video link and instruct an onboard paramedic, critical care nurse and CT technologist on treatment. This new technology should improve the speed of medical care, which is important as strokes quickly damage and kill brain cells.

2. Dengue fever vaccine

The World Health Organization reports that about half of the world's population is now at risk for dengue fever, which up until now was preventable only by avoiding mosquito bites. The disease is a leading cause of death and illness in children in some countries. A new vaccine has been developed and tested, and is expected to be available in 2015.

3. Painless blood testing

For those who hate large needles, a nearly painless way to sample blood will be a welcome relief. Plus, it will be cheaper and provide faster results than today's blood test. The new technology takes blood from your fingertip, and the Cleveland Clinic reports that over 100 tests can be performed on just one drop of blood.

4. New way to lower cholesterol

New self-injectable drugs called PCSK9 inhibitors have shown to be very effective in lowering cholesterol. These drugs may prove to be helpful for people with high LDL cholesterol who don't have good results with statins. The FDA is expected to approve the first PCSK9 in 2015.

5 ways to lower cholesterol

5. Cancer drug that doesn't harm healthy tissue

Although chemotherapy can save lives, it can be hard on the body and attack healthy cells as well as cancerous ones. A welcome breakthrough in the world of cancer treatment, antibody-drug conjugates can deliver targeted treatment without damaging healthy tissue.

6. Immune booster for cancer patients

Immune checkpoint inhibitors have been shown to prevent cancer cells from "hiding" from the immune system, allowing the body to more effectively fight these abnormal cells. Combined with chemotherapy and radiation treatment, the drugs have shown significant, long-term cancer remissions for patients with metastatic melanoma, one of the most deadly forms of cancer.

7. Wireless cardiac pacemaker

Until this point, wires have been a necessary component in pacemakers. A new wireless pacemaker about the size of a vitamin can now be implanted in the heart without surgery. Its lithium-ion battery is estimated to last about seven years.

8. New medications for idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis is a life-threatening disease that causes scarring in the lungs, leading to breathing difficulties and a shortage of oxygen in the brain and other organs. Life expectancy is only three to five years after diagnosis, but those numbers may change now that the FDA has approved two experimental drugs that slow the disease: pirfenidone and nintedanib.

9. Single-dose radiation therapy for breast cancer

The National Cancer Institute estimates that 40,000 women in the United States will die from breast cancer in 2014. The Cleveland Clinic cites multiple chemotherapy appointments, sometimes requiring the patient to travel long distances, as a hindrance to successful treatment. Intraoperative radiation therapy is a new solution. It treats a breast cancer tumor during surgery in a single dose, reducing time and cost spent on treatment.

10. New drug for heart failure

About 5.1 million people in the United States suffer from heart failure, according to the National Heart, Lung and Blood Institute. It is managed with a combination of drugs, but a new drug, angiotensin-receptor neprilysin inhibitor, has been granted fast-track status by the FDA because of its ability to cut the risk of dying from heart failure more effectively than current treatments.

For more information on the annual medical innovations list, including descriptions and videos, download the "Innovations" app or visit the website. A "where is it now" feature also includes updates on innovations that made the top 10 list in prior years.

"We look in past to see what we voted on to improve the process," Roizen said. "With one exception, we've been pretty good."

Source: www.cnn.com

By Catharine Paddock PhD

At present, diagnosis of lung cancer relies on an invasive biopsy that is only effective after tumors are bigger than 3 cm or even metastatic. Earlier detection would vastly improve patients' chances of survival. Now a team of researchers is developing a "lab-on-a-chip" that promises to detect lung cancer - and possibly other deadly cancers - much earlier, using only a small drop of a patient's blood.

In the Royal Society of Chemistry journal, Yong Zeng, assistant professor of chemistry at the University of Kansas, and colleagues report a breakthrough study describing their invention.

For some time, scientists have been excited by the idea of testing for disease biomarkers in "exosomes" - tiny vesicles or bags of molecules that cells, including cancer cells - release now and again. When they first spotted them, researchers thought exosomes were just for getting rid of cell waste, but now they know they also do other important things such as carry messages to other cells near and far.

The challenge, however, is developing a technology that is small enough to target and analyze the contents of exosomes - mostly nucleic acids and proteins - to find unique biomarkers of disease. This is because exosomes are tiny - around 30 to 150 nanometers (nm) in diameter - much smaller, for example, than red blood cells.

Current methods for separating out and testing exosomes require several steps of ultracentrifugation - a lengthy and inefficient lab procedure, as Prof. Zeng explains:

"There aren't many technologies out there that are suitable for efficient isolation and sensitive molecular profiling of exosomes. First, current exosome isolation protocols are time-consuming and difficult to standardize. Second, conventional downstream analyses on collected exosomes are slow and require large samples, which is a key setback in clinical development of exosomal biomarkers."

Now, using microfluid technology, he and his colleagues have developed a lab-on-a-chip that can analyze the contents of targeted exosomes and spot the early signs of deadly cancer. They have already successfully tested it on lung cancer.

Lab-on-a-chip device uses smaller samples, is faster, cheaper and more sensitive

The new device, which uses much smaller samples, promises to produce results faster, more cheaply, with better sensitivity compared to conventional benchtop instruments, as Prof. Zeng continues to explain:

"A lab-on-a-chip shrinks the pipettes, test tubes and analysis instruments of a modern chemistry lab onto a microchip-sized wafer."

The technology behind the device - known as microfluidics - came out of new semiconductor electronics and has been under intensive development since the 1990s, he adds:

"Essentially, it allows precise manipulation of minuscule fluid volumes down to one trillionth of a liter or less to carry out multiple laboratory functions, such as sample purification, running of chemical and biological reactions, and analytical measurement."

Unlike breast and colon cancer, there is no widely accepted screening tool for lung cancer, which in most cases is first diagnosed based on symptoms that normally indicate lung function is already impaired.

To diagnose lung cancer, doctors have to perform a biopsy - remove a piece of tissue from the lung and send it to a lab for molecular analysis. It is rarely possible to do this in the early stages as tumors are too small to be spotted on scans.

"In contrast, our blood-based test is minimally invasive, inexpensive, and more sensitive, thus suitable for large population screening to detect early-stage tumors," says Prof. Zeng, adding that the technique offers a general platform for detecting exosomes from cancer cells. The team has already used the device to test for ovarian cancer, and in theory, says Prof. Zeng, it should also be applicable to other cancer types.

"Our long-term goal is to translate this technology into clinical investigation of the pathological implication of exosomes in tumor development. Such knowledge would help develop better predictive biomarkers and more efficient targeted therapy to improve the clinical outcome," he adds.

The team has received further funding from the National Cancer Institute at the National Institutes of Health to further develop the lab-on-a-chip.

In March 2013, Medical News Today learned how another team of scientists is developing a lab-on-a-chip that is implanted under the skin to track levels of substances in the blood and transmit the results wirelessly to a smartphone or other receiving device.

Source: www.medicalnewstoday.com

By Caleb Hellerman

Earlier this week, Brian Shepherd sat down in a small doctor's office in Bethesda, Maryland. A technician swabbed his arm and gave him a quick jab with a needle.

With that, Shepherd became subject No. 13 in the experiment testing a potential Ebola vaccine.

The trial was launched on an emergency basis earlier this month by the National Institute on Allergy and Infectious Disease. It's the first to test this kind of Ebola vaccine in humans.

"It's not just for the money," Shepherd wrote in a Reddit AMA. "I'm very interested in translational research and experiencing it from the guinea pig side is very rewarding. But yeah, the money helps. This one study will fund most of my grad school application costs, though not in time for application season."

The vaccine doesn't use live virus and can't infect volunteers with Ebola. Instead it uses specific Ebola proteins to trigger an immune response. They're delivered through the body on a modified version of an adenovirus, a type of cold virus.

In the initial phase, 10 healthy volunteers were given a low dose of vaccine. They were monitored for side effects and tested to see if their bodies are producing antibodies. In the second phase, of which Brian is a part, an additional 10 volunteers are being given a higher dose.

All participants will be followed for nearly a year and tested at regular intervals.

Shepherd, who has volunteered for several prior research studies at NIH, spoke with CNN about his experience.

The following is a condensed version of that conversation:

CNN: How did you come to join the study?

Brian Shepherd: I actually work at NIH; I'm a post-doc researcher in a developmental biology lab. Most trials I learn about from reading a ListServ (email list).

I heard about the vaccine study from going to preliminary meetings for a different study.

CNN: When was this?

Shepherd: Less than a month ago. I had my first appointment on August 26. It was just a sit-down, to talk about the trial, go through paperwork and consent forms, explaining what the trial was for. Then they did an initial run-through of my health history.

CNN: What was next?

Shepherd: The next week I had my second appointment. They did a full physical, blood work, health history, breathing checks. A lot of poking and prodding. My third visit was Wednesday. They drew blood, then gave me a shot. Now, my next appointment is Sunday.

CNN: What was it like? You wrote that pulling off the Band-aid was the worst of the pain.

Shepherd: I'm supposed to keep a daily diary for the first seven days, logging my temperature and any symptoms. The next morning, I woke up with a slight fever, 100.5. I took some Tylenol and it went away.

Other than that I feel fine. In fact, I ran a half-mile in a relay race at lunchtime with some people from work.

CNN: You wrote that for each of these regular visits, you're paid $175. How many times have you been a human guinea pig?

Shepherd: This is my second drug trial. Before that, I did mostly MRI studies.

The first one I did, I was in the MRI machine and had three tasks. They gave me two buttons and showed pictures. If it was Spiderman, I'd hit one button; if it was the Green Goblin, I'd hit the other. So I spent 15 minutes playing Spiderman vs. Green Goblin.

CNN: Did you have any reservation at all, taking part in this Ebola vaccine trial?

Shepherd: None at all.

Source: http://www.cnn.com

By Associated Press

New York state can end its three-decade HIV crisis by the year 2020, Gov. Andrew Cuomo said Sunday as he announced an ambitious plan to deliver a knockout blow to the epidemic by boosting testing, reducing new infections and expanding treatment.

The governor said the state is aiming to reduce new HIV diagnoses to 750 by the end of the decade - about the same number of tuberculosis cases seen in New York City each year - down from 3,000 expected this year and 14,000 new cases of the disease in 1993. If the state is successful, it would be the first time the number of people living with HIV has gone down since the crisis began with the first widely reported cases in 1981.

"Thirty years ago, New York was the epicenter of the AIDS crisis," Cuomo said. "Today I am proud to announce that we are in a position to be the first state in the nation committed to ending this epidemic."

To expand treatment, the state's Department of Health has negotiated bulk rebates with three companies producing HIV drugs. The state is also taking steps to make it easier to get tested, changing how HIV cases are tracked to ensure patients continue to receive treatment, and boosting access to "pre-exposure" drugs that can help high-risk people avoid infection.

Cuomo did not offer an estimate of the cost of the plan, but said it would end up saving the state more than $300 million per year by 2020 by reducing the amount the state pays for medical care for those with HIV.

Groups that have long advocated for HIV patients praised the governor's announcement, saying it shows that efforts to fight the disease are paying off, and that a scourge that once seemed unbeatable can be successfully fought.

"We have the tools and know-how to end the AIDS epidemic in New York, the only question is whether we have the political will," said Jason Walker, an organizer at VOCAL-NY, which advocates for low-income HIV patients. "Even without a vaccine or cure, Cuomo understands that we can dramatically reduce new infections below epidemic levels and ensure all people living with HIV achieve optimal health."

While the state's plan may sound overly optimistic, the number of new HIV cases in New York has dropped nearly 40 percent in the last 10 years because of better, faster tests; access to condoms; public outreach campaigns and other initiatives. Meanwhile, those with the disease are living longer thanks to significantly more effective treatments.

The goal of bringing the disease to below epidemic levels "is ambitious," said Mark Harrington, executive director of the anti-HIV organization Treatment Action Group, but "grounded in reality."

Source: foxnews.com