“This year doesn’t look like it’s going to be tremendously unusual in terms of overall cases of mosquito-borne diseases,” said Jonathan Day, a professor of medical entomology with the University of Florida’s Institute of Food and Agricultural Sciences. “But transmission of [EEEV] tends to be very focal, and there are some areas that are looking risky.”

EEEV is best known for being deadly in horses, but humans can contract the virus as well.

According to the national Centers for Disease Control and Prevention, the virus can cause a severe infection of the central nervous system in humans, and is fatal for nearly a third of those afflicted.

So far this year, 26 horses have been found to be infected in North Florida, with five more in the state’s Panhandle.

These cases, along with analysis of weather conditions and other indicators, have led UF entomologists to believe that a band of counties beginning at Volusia County and stretching northwest into the Florida Panhandle carry a moderate to high risk of mosquitoes carrying the virus.

For an up-to-date risk map, please visit http://eis.ifas.ufl.edu/eis1.htm.

“July is usually the peak for EEEV transmission,” said Roxanne Connelly, an IFAS professor of medical entomology. “We’ve had the type of weather patterns that can make the problem worse in some areas.”

The disease is spread via mosquitoes that have fed on birds. Humans and horses cannot spread the virus to other humans and horses.

Connelly advises that people in risk areas avoid being outside during peak feeding times for mosquitoes that carry the disease — calm, humid periods from dusk to dawn.

If you are outside during these times, you should cover as much skin as possible. Bare skin should be treated with a repellent that carries DEET or Picaridin.

“There are all sorts of traps and tools out there like bug lights and citronella candles,” Connelly said. “None of them keeps mosquitoes from biting you — only a repellent applied directly on your body can do that.”

Pet birds should be kept inside and, while it is very rare for dogs and cats to contract EEEV, Connelly suggests being aware that pets aren’t immune to pesky mosquito bites.

Spraying dogs and cats with repellents labeled for use on humans can be dangerous because they can lick the repellent while grooming. There are products made for dogs that do not contain DEET, but make sure to read and follow the directions.

Pets are best kept inside away from mosquitoes during peak feeding times. And, any dog that is at risk of being bitten should be on a monthly heartworm prevention treatment. Prevention treatments formulated for cats are also available.

GAINESVILLE, Fla. — Coffee and tea drinkers, take note — a University of Florida study says a beverage made from a native holly tree might be just the thing to give you a caffeinated kick-start, plus a dose of antioxidants.

Yaupon (YO-ponn) holly is the only U.S. plant that produces substantial amounts of caffeine, said Jack Putz, a botany professor affiliated with UF’s Institute of Food and Agricultural Sciences. A popular ornamental species, yaupon grows wild throughout the Southeast and can be grown in most coastal states.

Centuries ago, American Indians and Spanish settlers steeped yaupon leaves and twigs in hot water to make a stimulating beverage, but that use of the plant is virtually unknown today.

The resulting brew is dark brown and tastes much like green tea. If it makes a comeback, yaupon may spawn a cottage beverage industry, Putz said. And the antioxidants might be useful in nutritional supplements.

“A few years ago we were contacted from a pharmaceutical company in Texas,” he said. “At first, we thought their interest was in caffeine but they said that with all the decaffeinated beverages around, caffeine is cheap. What they were interested in was the antioxidants.”

Nitrogen fertilizer can boost yaupon production and caffeine content, according to a paper Putz co-wrote, published in this month’s issue of the journal Economic Botany. Nitrogen had little effect on antioxidant content.

The researchers focused on a popular ornamental yaupon variety called Nana, said Matt Palumbo, a botany master’s graduate and co-author of the paper. After receiving nitrogen fertilizer, Nana plants yielded 35 percent more leaves; caffeine concentration in the leaves shot up 265 percent.

Nana had about half the antioxidant content of green tea, he said.

“I have found genotypes with antioxidant concentrations at least as high as green tea,” Palumbo said.

Similarly, Nana’s caffeine content was low compared with concentrations reported in previous studies, he said.

Dry, unprocessed yaupon leaves contain between .65 percent and .85 percent caffeine by weight. Coffee beans are about 1.1 percent caffeine by weight and tea leaves about 3.5 percent caffeine.

More research is needed to learn which yaupon varieties have the greatest caffeine and antioxidant content, Palumbo said. Afterward, new cultivars can be developed.

One point seems clear — if U.S. residents begin drinking yaupon tea it could reduce demand for coffee, which may ease ecological pressure on coffee-farming regions of South America, Africa and Southeast Asia, he said.

It’s uncertain whether large-scale yaupon farming would be economically feasible in the U.S., but the antioxidants appear to have commercial potential, he said. And home gardeners might enjoy growing and using yaupon.

One caveat — before making yaupon tea it’s critical to obtain the correct plant, Putz says. There are numerous U.S. holly species, many of them not safe for consumption.

The taste of yaupon tea will be the make-or-break factor for potential users, says Dan Austin, an ethnobotanist based at the Arizona-Sonora Desert Museum in Tucson.

If they don’t like the flavor — something Austin says is quite possible — then they’re unlikely to drink the beverage regardless of the health benefits.

Still, he says, “if the proper spin is put on it, the potential is there.”

GAINESVILLE, Fla. — “What brings you in to see me today?”

“Part of my left breast has been painful for awhile.”

“Can you lie down so that I can examine you?”

It sounds like a snippet of conversation between doctor and patient. But the doctor, in this recent exchange at the University of Florida campus, was actually an engineering doctoral student — and the patient a “mixed reality human” composed of a life-sized computer avatar on a flat screen and a mannequin with a prosthetic breast.

Intimate procedures such as breast exams, while a routine and critical part of medical care, are notoriously tough to teach. Medical students practice on disembodied prosthetics but have limited opportunities to practice exams on real people — especially patients who have an abnormality. In a collaboration with the Augusta, Ga.-based Medical College of Georgia and three other universities, UF engineers have crafted a solution: a hybrid computer/mannequin that helps train students not only how to correctly perform a breast exam — but also how to talk to, and glean information from, the patient during the procedure.

The project is important because correct examinations and good doctor-patient communication are critical to successful medical treatment, said Benjamin Lok, a UF assistant professor of computer and information sciences and engineering who heads the effort.

“Studies have shown that communication skills are actually a better predictor of outcome than medical skills,” Lok said. With the virtual patient, “all of a sudden, students have to not only practice their technique, but they also have to work on their empathy.”

The mixed reality human, named Amanda Jones, “talks” to students, and they respond via a computer speech and voice recognition system tailored by doctoral student Aaron Kotranza, Lok and others on the team. Her physical form — a mannequin — is immobile, but her virtual representation, created by the engineers, moves and speaks from a large flat screen above her physical body. Students can also view Jones through a head-mounted display.

The interaction is unscripted, but it follows a typical pattern for a woman’s visit and examination — with both verbal and tactile challenges for the medical students.

The student must tease out Jones’ medical history, listen to her concerns and respond to her questions. Just as in a real exam, this interaction occurs simultaneously with the physical examination. For that, the student must use the correct palpitating technique and apply the proper pressure. Sensors within the prosthetic breast — developed by Dr. Carla Pugh at Northwestern University — provide pressure information depicted by colors on the virtual breast, guiding students in the exams. The engineers can program the system to include or exclude an abnormality — and the attendant conversation.

It sounds awkward, and to be sure, the speech recognition element has its hiccups.

But especially for students reared in an era of sophisticated three-dimensional video games, the system turns out to be surprisingly convincing. The researchers have tested it on about 100 medical students so far, all from the Medical College of Georgia, where co-principal investigator Dr. D. Scott Lind is based. One of their most consistent and prominent findings: Students do not hesitate to express empathy to Jones.

“We have found that they will try to comfort the virtual human,” Kotranza said. “They’ll often touch the mannequin in order to comfort her.”

A pilot study has concluded that students who practiced with a mixed realty human improved their communication skills and their technical abilities, but more trials are needed to determine whether those skills persist once the students examine real patients.

That said, it seems obvious that more practice students get, the better off they will be. Lok said the mixed reality patient is not intended to replace real volunteers - far from it. But students typically have only a handful of opportunities with those volunteers before graduating. The mixed reality patient can add to their training while making it easier for teachers to help students with both their conversational and medical techniques.

“What happens if you find something in a woman’s breast? How do you talk to the patient?” Lok asked. “Students have to somehow build their database of experience.”

While the breast exam research continues, the team also intends to explore other intimate exams. Next in line: prostate exams. Lok and the students already have prosthetics they intend to couple with a virtual male patient similar to the breast exam patient.

The other institutions participating in the project are the University of Central Florida, the University of Georgia and Northwestern University. The research, part of a larger effort involving a number of different virtual patient projects, is supported by grants of about $2.8 million primarily from the National Science Foundation and the National Institutes of Health.

Two University of Florida scientists are part of the multicenter team of researchers that made the discovery, which could pave the way for better treatments that target the disease, according to findings published Wednesday in the journal Nature.

“What makes our study so important is that although neuroblastoma accounts for 7 percent of childhood cancers, it is responsible for 15 percent of deaths in children with cancer,” said Wendy London, a research associate professor of epidemiology, biostatistics and health policy research at the UF College of Medicine and a member of the UF Shands Cancer Center. “This paper adds yet another gene in the pathway that could lead to tumorigenesis (tumor formation) of neuroblastoma.”

Neuroblastoma forms in developing nerve cells, with tumors most often found on a child’s adrenal gland. It’s the most common form of cancer in babies and the third most common childhood cancer, according to the American Cancer Society.

Led by Dr. John J. Maris, director of the Cancer Center at The Children’s Hospital of Philadelphia, researchers performed what’s known as a genome-wide association study to uncover errors in DNA that could be associated with neuroblastoma.

To do this, researchers analyzed the genetic makeup of 846 patients with neuroblastoma, whose samples were derived from the Children’s Oncology Group Neuroblastoma Tumor Bank, and 803 healthy patients in a control group.

On the basis of their initial findings, the researchers performed a second validation analysis, pinpointing that a glitch called a “copy number variation” in a single chromosome is associated with neuroblastoma. Copy number variation has to do with the gain, loss or duplication of snippets of DNA.

“This is part of series of papers that creates the bigger picture, an understanding of the genetic mechanisms that lead to neuroblastoma,” said London, the principal investigator for the Children’s Oncology Group Statistics and Data Center at UF. “We are searching for genetic targets to treat with therapy.”

The researchers reported additional genetic links in Nature Genetics in May. The team discovered that on the gene called BARD1, six single-nucleotide polymorphisms — variations in tiny pieces of DNA — were also associated with neuroblastoma.

“Only two years ago we had very little idea of what causes neuroblastoma,” said Maris, who led both studies. “Now we have unlocked a lot of the mystery of why neuroblastoma arises in some children and not in others.”

Although neuroblastoma is one of the more common childhood cancers, it is relatively rare overall when compared with more common adult cancers, which has proved to be a challenge for researchers trying to uncover its causes, said Dr. Peter Zage, an assistant professor of pediatrics at the Children’s Cancer Hospital at the University of Texas M.D. Anderson Cancer Center.

“Dr. Maris’ group has been able to collect a relatively large number of cases for a neuroblastoma study and so has been able to identify these genetic variations and specific genes to provide us with some new avenues for therapy that we probably would not have been able to identify looking at the smaller cohorts of patients we each see at our individual institutions. In that sense, it’s certainly an amazing leap forward in our understanding of the disease.”

The discovery does hold promise for developing treatments, but London cautions that these potential “targeted therapies” won’t work on all neuroblastoma patients. Not all neuroblastoma patients have this particular genetic anomaly, and not all children with this anomaly will develop neuroblastoma. Development of neuroblastoma is complicated and can occur because of multiple reasons, arising after a complex chain of events, London said.

“What’s amazing is there are so many different ways for tumorigenesis to occur,” London said. “That’s the reason it is so hard to treat and cure cancer, or even to understand why it happens and how it happens.”

All the researchers involved in the study are members of the Children’s Oncology Group, the only National Institutes of Health/National Cancer Institute pediatric cancer cooperative group. The group performs clinical trials, collects specimens and performs statistical analysis related to pediatric cancers. UF is one of three institutions with a COG Statistics and Data Center, where study design, data collection and statistical analysis for COG research occurs.

Wait times to receive a deceased donor kidney transplant have increased over the years, but this study is the first to define and quantify what this wait time means for older patients. Researchers suggest that some candidates should consider live-donor options rather than wait for deceased-donor organs to become available.

The findings give firm data that can guide patients in making decisions, and policymakers in allocating donated organs.

“If someone knows that they have a 10 percent chance of dying before transplantation, they might consider it differently than if they know they have an 80 or 90 percent chance,” said Jesse Schold, an assistant professor of medicine and first author of the paper published today (June 18) in the Clinical Journal of the American Society of Nephrology. “Understanding what these survival estimates are may provide a more objective and useful basis for evaluating donor options for this population.”

The researchers suggest that some patients need to ask their doctors about their chances of surviving to receive a transplant, and, once they decide, to speed through the steps necessary to get on the waiting list. It can take several months for patients to go from primary care provider referral to a transplant center and through the medical tests and additional steps involved in getting their name on the list.

“Older patients must be referred for transplantation sooner than they are now, and they need to be guided through the process of pursuing live donor kidney transplantation,” said Harvard transplant psychologist Jim Rodrigue, director of behavioral health services and research in the Transplant Institute at Beth Israel Deaconess Medical Center. “The older population is least likely to pursue a live donor transplant and is less likely to have healthy living donors available.”

That’s because the older people get, the older their siblings and peer network become, with potentially more medical problems than when they were younger. And older patients tend to say they do not want to burden their adult children, other relatives or friends by asking them to be live donors.

About 50 percent of the more than half a million people in the United States who have end-stage renal disease are older than 60. In medically eligible patients, kidney transplantation gives a better survival chance than dialysis.

The UF team examined data from the national Scientific Registry of Transplant Recipients for almost 55,000 candidates older than 60 who were listed for a single-kidney deceased-donor transplant from 1995 through 2007. They used statistical models to estimate the time to receive a transplant and time to death after getting on the list.

Although overall about half of the over-60 group was projected to die before transplant, different subgroups had even higher likelihood of dying before a transplant.

Long-standing racial disparities are borne out by the data, with black patients having a higher probability than white patients of dying before a transplant: Sixty-two percent of black patients older than 60 will likely die before getting a transplant.

“That is an important finding because African-Americans are substantially less likely than whites to receive a live donor transplant, regardless of age,” Rodrigue said. “For those who are over 60, this is simply more bad news.”

Another notable disparity is that people’s survival chances vary greatly — from 8 percent to 81 percent — depending on where in the country they happen to live.

“It seems inherently unjust that we have such significant geographic disparity in survival on the waiting list based on where you live,” Rodrigue said.

It is true that some regions are better than others at recovering organs and have better donor rates. But based on the study’s results, one thing for policymakers to consider might be redrawing geographical boundaries of designated transplant regions so that more people have a better shot at getting an organ.

“We like to promote equity and policies that give a fair chance,” Schold said.

While the study findings support broad conclusions about patients’ survival chances, they might not apply to individual patients.

Still, Rodrigue said, they will change the doctor-patient conversations at his institute, for one. In the past, the underlying assumption was that patients will eventually get a deceased donor organ.

“Now we’ll have a more directed conversation with patients about the risk of death,” he said. “It’s not just how long you wait.”

GAINESVILLE — For most parents, soothing a child’s anxiety is just part of the job. But for a parent whose child has obsessive-compulsive disorder, soothing anxiety and helping with behaviors linked to the disease could lead to more severe symptoms, University of Florida researchers say.

Often, parents of children with OCD will help their children complete rituals related to their obsessions and compulsions, such as excessive bathing or checking things like door locks, according to findings recently published in the Journal of Consulting and Clinical Psychology. These accommodations can be anything that makes the symptoms of OCD less impairing, from reassuring a child that his hands are clean and his baby brother is OK to even doing his homework for him or buying objects that make the child feel safe.

“Parents do that because that is what a parent whose child doesn’t have OCD would do,” said Lisa Merlo, a UF assistant professor of psychiatry and the lead author of the study. “If your child is upset, you try to comfort them. But what we know is, for patients with OCD, if they get an accommodation, that reinforces the OCD to them.

“It’s validating the OCD in the kid’s mind, and that’s what you don’t want to do.”

About one in 200 children and teenagers in the United States have OCD, according to the American Academy of Child & Adolescent Psychiatry.

The study included 49 children between 6 and 18 with OCD and their families who came to UF for a type of treatment called cognitive-behavioral therapy. This form of therapy involves exposing children to their fears and teaching them better ways to respond and cope. During the sessions, therapists teach parents how they should deal with their child’s OCD, too.

Prior to the start of the 14-session therapy, the researchers gauged how severe each child’s condition was and compared it to how many accommodating behaviors parents reported. They found that the more severe the child’s OCD, the more the child’s family seemed to accommodate OCD behaviors.

“You would think if parents are helping, the kids would be less impaired,” Merlo said. “But what we are seeing is that it snowballs and makes it worse and worse.”

After the treatment, researchers noticed a significant decrease in how often families were assisting children with OCD behaviors and rituals. Children whose families had the biggest decrease in these accommodations also had the biggest improvement in their OCD symptoms, Merlo said.

What researchers don’t yet know is if a family’s “help” causes a child’s OCD to worsen or if the severity of the disease causes parents to try to do more to help their children.

Some children, including many who come to UF’s clinic, have symptoms so severe it prevents them from playing with friends or even going to school, Merlo said. In these instances, parents often feel they have to do whatever they can to help their children function, from doing their homework for them to buying specific items they feel like they need.

“If a kid is struggling a lot, parents feel like they have to do a lot to get through the day,” Merlo said. “But if the child is not experiencing the natural consequences of the OCD symptoms, then they don’t have any motivation to stop.”

This phenomenon isn’t exclusive to children and parents, said Jonathan S. Abramowitz, an associate professor and associate chairman of psychology at the University of North Carolina at Chapel Hill.

“We see it with adults’ spouses and partners, too. In trying to be helpful to the person with OCD, they end up making the problem worse.”

Although therapists have noticed this phenomenon anecdotally, there has so far been little research evidence to prove it. UF’s study will help therapists and scientists address the problem, he said.

“It is very nice to have research data to back up these clinical observations,” he said.

Researchers with the McKnight Brain Institute of the University of Florida, in collaboration with scientists at the University of Frankfurt, Germany, discovered that inflammation of microglia — an abundant cell type that plays an important supporting role in the brain — does not appear to be associated with dementia in Alzheimer’s disease.

The finding supports recent clinical trial results that indicate anti-inflammatory drugs are not effective at fighting dementia in patients with Alzheimer’s disease, which affects about 5.3 million Americans.

“For almost 20 years now, it’s been claimed that brain inflammation contributes to the development of Alzheimer’s disease dementia, and based on that claim, numerous clinical trials with anti-inflammatory drugs have been conducted. They have been unsuccessful,” said Wolfgang Streit, a professor of neuroscience at the College of Medicine. “In the current paper we have shown that the brain’s immune system, made up of microglia, is not activated in the brains of Alzheimer’s patients, as would be the case if there were inflammation. Instead, microglia are degenerating. We claim that a loss of microglial cells contributes to the loss of neurons, and thus to the development of dementia.”

Microglial cells are a subset of a very large population of brain cells known as glial cells. Neurons are the workhorse cells of the brain, enabling thought and movement, but glia are their faithful sidekicks, providing physical and nutritional support.

Glial cells, which outnumber neurons 10-to-1, are at the heart of a popular explanation for Alzheimer’s disease that suggests protein fragments called beta amyloid — Abeta for short — clump together in the spaces between brain cells, causing memory loss and dementia. Inflammation theories suggest that microglia become “activated” and mount an immune response to these protein clumps, and instead of being helpful, a toxic release of chemicals occurs, worsening the disease effects.

However, Streit’s high-resolution observations did not find evidence that Abeta activates, or inflames, human microglia cells. Nor did researchers find evidence that inflammation is to blame for brain cell death.

“This paper potentially represents a paradigm shift in the way we look at Alzheimer’s disease,” said Mark A. Smith, a professor of pathology at Case Western Reserve University and editor-in-chief of the Journal of Alzheimer’s Disease. “The study goes against the very popular idea of neuro-inflammation; instead, the idea that microglia are senescent is consistent with a number of features of the disease.

“The research makes a very good case that these cells are subject to aging,” said Smith, who did not participate in the study. “These cells were thought to be activated (against Alzheimer’s), but this paper makes a strong case that they are not. The study has taken a novel approach that has led to a novel insight.”

Using a commercially available antibody, Streit for the first time created a marker for microglial cells in human brain specimens that had been in chemical storage. The specimens were from 19 people with varying degrees of Alzheimer’s, ranging from severe to none at all. Two of the samples were from Down syndrome patients, who are known to develop Alzheimer’s pathology in middle age.

When researchers examined these cells alongside neurons under a high-resolution microscope, they found that — unless an infection had occurred elsewhere in the body — microglial cells from Alzheimer’s patients were not distinctly larger or unusually shaped, which would have been the case had they been inflamed.

“What I expected to see is activated microglia right next to dying neurons,” Streit said. “That is what I did not find. What I propose is glia are dying, and the neurons lose support. We now need to find out what caused glia to degenerate. Rather than trying to find ways to inhibit microglia with anti-inflammatory drugs, we need to find ways to keep them alive and strong. It’s a whole new field.”

The microglial cells had a tangled, fragmented appearance, similar to neurons in the throes of Alzheimer’s disease or — old age.

“These cells are breaking into pieces,” said Streit, who collaborated with Alzheimer’s researcher Dr. Heiko Braak, of the Institute for Clinical Neuroanatomy in Frankfurt. “They are on their way out. For the first time, we are proving that microglial cells are subject to aging and may undergo degeneration, and that the loss of these cells precedes the loss of neurons. Research has been so focused on finding activated microglia, no one considered that these cells were degenerating and neurons lost support.”

The work was supported by the National Institutes of Health, the German Research Council and the Evelyn F. and William L. McKnight Brain Institute.

Alzheimer’s disease is the sixth leading cause of death in the United States and the fifth leading cause of death for Americans 65 and older, according to the Alzheimer’s Association. The association estimates Alzheimer’s and other dementias cost Medicare, Medicaid and businesses a total of $148 billion annually.

In mice implanted with human colorectal cancer cells, tumor volume decreased 53 percent and cancer cell growth slowed by 49 percent in those treated with a gene that encodes for the artificial protein, compared with those that were untreated.

The research team, led by Dr. Bradley S. Fletcher, an assistant professor of pharmacology and therapeutics in the College of Medicine, created the so-called fusion protein to target another protein called tumor endothelial marker 8, or TEM8, which was recently found to be preferentially expressed in the inner lining of tumor vessels. Such differences in protein expression enable delivery of drug molecules to the cells that harbor these proteins.

“The protein we created did a very good job of homing to the tumor and binding,” said Stephen Fernando, who recently completed his doctoral studies. “By targeting TEM8, we can potentially create a therapy against cancer.”

The Fletcher group is the first to target cancer cells through protein binding to TEM8. The findings, now available online, are featured on the cover of the June 15 edition of Cancer Research.

“If you can cut off the blood supply, then you can inhibit the tumor from growing — there have been many attempts,” said Brad St. Croix, director of the National Cancer Institute’s Tumor Angiogenesis Section, whose group first identified the TEM genes that over-express in tumor endothelial cells. “The concept of targeting tumor blood vessels has been around for many years, but it’s good that we’re finally getting around to the stage where we can see the vessels being targeted therapeutically — it’s pretty exciting, I think.”

St. Croix was not part of the current research team, but donated some experimental materials.

The UF group created a “fusion protein” — part of which binds to TEM8, and the other which promotes thrombosis, or blood clotting — and delivered genes that encode for it to the lungs of mice. The delivery vehicle was a transposon called Sleeping Beauty, a piece of DNA that can insert new genes stably and efficiently into a cell’s genome.

The lungs then functioned as a factory to produce the protein that later found its way to the target cells in the tumor vessels.

“We felt that TEM8 was an ideal target because it was inside the vessel, preferentially expressed there and unique,” Fletcher said.

In addition to promoting blood clots, the strategy also resulted in reduced tumor vessel density, possibly by interfering with TEM8 function.

Fletcher’s group previously applied the Sleeping Beauty transposon gene delivery method to the treatment of hemophilia and pulmonary hypertension and the prevention of lung transplant rejection in animal studies. After developing those three successful models, they looked for disease applications in which poor outcomes would be worth the risk associated with gene therapy.

“We felt that cancer was potentially a target,” Fletcher said. “Gene therapy has a lot of risk associated with it, so you don’t want to do it for diseases that are not life-threatening.”

The group plans to come up with a method to increase the amounts of the thrombosis-inducing protein produced in the body, and test whether higher dosing leads to unintended blood clots.

They are also looking into ways to deliver the protein directly to the sites of interest, rather than through genes that later produce the protein, and apply the method in other areas such as prostate cancer. Other work will include the use of coated nanoparticles to detect tumors and deliver drugs or radiate heat to destroy cancer cells when bombarded by radio waves.

The work was supported by a grant from the James and Esther King Foundation, and a travel grant for Fernando from the American Society of Gene Therapy.

Initial research suggested that enlargement and abnormalities of axillary sentinel lymph nodes — located in the armpit area near the breast — were predictive of cancer. But a University of Florida Shands Cancer Center researcher says it’s not the size of the node or enhancement, but the loss of a key part of a normal node’s structure called the fatty hilum that more accurately signals the spread of disease. The findings are available online in the Journal of Magnetic Resonance Imaging.

In addition to changing ideas about what doctors should look for while evaluating lymph nodes, the finding reinforces the value of using MRI to determine the extent of breast cancer prior to surgery.

“We found that the loss of fatty hilum in an axillary lymph node on MRI correlated with finding the spread of breast cancer in axillary nodes at the time of surgery,” said Dr. Stephen Grobmyer, an assistant professor of surgical oncology and endocrine surgery at the UF College of Medicine, who noted that not all nodes without fatty hilum necessarily had cancer.

The UF study retrospectively examined 56 female patients ranging in age from 30 to 82. All women had a sentinel lymph node biopsy. Fifteen women had cancer in the nodes that required complete removal. Four of eight patients in whom a loss of fatty hilum was seen in an axillary node on MRI were found to have cancerous lymph nodes at the time of their breast surgery. By comparison, only 11 out of 48 patients, or 23 percent, with all fatty hilum in place had cancer.

Grobmyer said these findings provide surgeons with another tool to help personalize medicine and evaluate factors that could indicate whether cancer has spread prior to surgery.

“I think this is another step to understanding how we can use MRI to improve care of breast cancer patients,” said Grobmyer, medical director of the UF Comprehensive Breast Center. “We are just suggesting that there may be information that people have not yet paid attention to that may impact our understanding of the staging of a patient’s disease. With this technology, if you look and see there is a node or several nodes with no fatty hilum, one would be very suspicious that there might be metastatic disease present. Instead of doing an invasive sentinel node biopsy, one could do a less invasive image-guided biopsy to obtain important staging information.”

He added it is also important that we now understand that MRI features that suggest cancer in the breast do not apply for evaluating disease in axillary lymph nodes. Currently, there is no standard MRI criterion for determining if cancer is in the nodes.

Although not routinely administered to all breast cancer patients, magnetic resonance imaging, or MRI, can offer a detailed picture of the breast, providing precise details about breast cancer locations and size. The scan is augmented through a technique known as contrast enhancement, which makes it easier to discern between cancerous and healthy tissue. The standard scan includes the axillary lymph nodes, the most common first site of spread for breast cancer.

Dr. Steven E. Harms, a radiologist with the Breast Center of Northwest Arkansas, said the accurate diagnosis of lymph node metastases is critical for patients with breast cancer, and the ability to determine their presence before the initial surgery could spare many patients the need for more than one operation.

“Over-treatment with a full axillary node removal is associated with a high incidence of lymphedema, a lifelong and often debilitating condition resulting from the disruption of lymph channels,” said Harms, who, in 2007, helped to draft the American Cancer Society breast cancer screening guidelines which recommend breast MRI screening for high risk patients.

Grobmyer said he hopes studies of a larger number of patients will further validate these findings so they can be broadly applied. He said the great advantage of an MRI is its ability to pick up more than 95 percent of invasive breast cancers.

In late 2007, UF researchers presented findings about the diagnostic value of MRI in influencing treatment plans for women, citing that it can find previously undetected cancerous areas, including cancer in the opposite breast. MRI also helps to better determine tumor size and assess an individual’s response to chemotherapy, making it useful for planning surgical procedures, UF surgeons say.

Of more than 100 possible mutations of a single gene inherited by people with familial ALS, the mutations most inclined to produce clumps of problematic cellular debris known as “protein aggregates” appear to be associated with quicker progress of the disease, according to researchers with the University of Florida’s McKnight Brain Institute writing online this week in Human Molecular Genetics.

Meanwhile, in a separate study recently online in the Proceedings of the National Academy of Sciences, scientists describe how these protein clumps — long considered a defining characteristic of ALS — do not cause the disease, but appear later on, increasing in number between onset of weakness and paralysis in patients.

Together, these findings suggest that the deadly course of the disease is linked to the formation of these protein clumps, even though the sickness may have been well under way.

“Blocking aggregation of these proteins could be a therapeutic target for individuals with this genetic mutation,” said David Borchelt, a professor of neuroscience and director of the SantaFe HealthCare Alzheimer’s Disease Research Center at UF’s McKnight Brain Institute. “Right now, there is little that can be done to help these patients.”

ALS involves the death of nerve cells that stretch from the brain to the spinal cord, and from the spinal cord to muscles. It strikes people between the ages of 40 and 70, according to the ALS Association. An estimated 30,000 Americans have the disease at any given time.

Patients usually have a life expectancy of two to five years, with some notable exceptions, such as Cambridge University scientist and author Stephen Hawking, who has survived for more than 40 years since his diagnosis.

The cause of ALS is unknown in about 80 percent of cases, but 10 percent to 20 percent of ALS cases can be traced to an inherited genetic defect. No matter the cause, scientists believe that a basic cellular process in which amino acids are folded into proteins goes wrong in ALS. The misfolded proteins cannot perform their intended function. Instead, they form the troublesome protein aggregates.

UF’s research centered around one gene that produces an enzyme called superoxide dismutase 1, or SOD1. Although SOD1 performs an important role in cell maintenance by warding off dangerous molecules known as free radicals, 146 different mutations in the SOD1 gene have been identified in patients with inherited ALS.

UF scientists, including doctoral student Mercedes Prudencio with Dr. Peter Andersen of Umea University in Sweden, analyzed data from ALS patients to correlate the disease features with more than 30 different variants of SOD1. They found that the mutations most associated with protein aggregation are generally predictive of a more rapid disease progression.

In the PNAS study, UF researchers with investigators from the University of Texas Health Science Center in San Antonio pinpointed when the protein clumping begins and how long the disease has been at work before symptoms actually appear.

By studying SOD1 in mice genetically engineered with a form of ALS, UF doctoral student Celeste Karch demonstrated that the protein clumps appear in spinal cord tissues later in the disease, about the same time that symptoms appear, but well after cell damage occurs from nerve loss and the formation of fluid-filled pockets called vacuoles.

The finding suggests the aggregated proteins may elude normal cellular “housecleaning” methods, or their formation is heightened by stress conditions in the cell.

“As the disease enters the symptomatic stage in mice, the buildup of protein is rapid and dramatic,” Borchelt said. “However, the formation of these aggregates is not the whole story. It is well established that significant damage to the nervous system occurs well before the symptoms appear. The uncontrolled misfolding of SOD1 seems to be confined to the late stage of disease, which is when symptoms first appear, giving hope that treatments targeting this process could be beneficial.”

Furthermore, the findings suggest that there is a larger therapeutic window to treat ALS, if scientists can find a way to diagnose the disease before the hallmark protein clumping begins.

“Many scientists had accepted that protein aggregation was tied to the causation of ALS,” said Joan Selverstone Valentine, a UCLA professor of chemistry and biochemistry who did not participate in the study. “But this research shows these aggregates form during disease progression, not initiation. It is important to know what to look for as an early cause of the disease and what causes it to get more severe. That means we have to look for something upstream of aggregation as a cause, as well as understand the steps in the progress. If you can prevent or halt the aggregation, you can stop the disease in its tracks. That’s as good as a cure if it can be done early enough.”

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GAINESVILLE, Fla. — Call it a Breathalyzer for the hands.

Using sensors capable of detecting drugs in breath, new technology developed at University of Florida monitors health-care workers’ hand hygiene by detecting sanitizer or soap fumes given off from their hands.

By reminding workers to clean their hands to remove disease-causing organisms such as the bacteria MRSA, the system could help reduce hospital-acquired infections and save millions of dollars now spent to treat them.

The trademarked system, called HyGreen, logs, down to the second, the frequency of hand cleaning and contact with patients in a database that clinical supervisors can review immediately.

This is the first system that enables real-time monitoring of hand washing.

“This isn’t big brother, this is just another tool,” said Dr. Richard J. Melker, a UF College of Medicine anesthesiology professor who developed the technology along with professors Dr. Donn Dennis, and Dr. Nikolaus Gravenstein, of the anesthesiology department, and Christopher Batich, a materials science professor in the College of Engineering. “A hospital worker never wants to be responsible for someone getting sick or dying from an infection acquired in the hospital.”

HyGreen is now being tested in the Neuro Intensive Care Unit at Shands at UF medical center, and will be presented at the annual meeting of the Association for Professionals in Infection Control and Epidemiology June 6 to June 9 in Fort Lauderdale, Fla.

Here’s how it works: The health-care worker squirts sanitizer gel or soap into his or her hand before passing it under a wall-mounted sensor. A wireless signal from a badge worn by the worker activates a green light on the hand-washing sensor. When the worker enters a patient room, a monitor near the bed detects the status of the badge, and flashes green if the person has clean hands. If the person has not washed, or too much time has passed between washing and approaching the patient, the badge will give a gentle “reminder” vibration.

“I do wash my hands more often,” said registered nurse Carrie McGirr, who volunteered to help test the HyGreen system. “It’s a fairly simple process to learn.”

Close to 2 million hospital-acquired infections occur each year and more than 250 related deaths occur each day in the United States, according to the Centers for Disease Control and Prevention.

“A substantial number of those are preventable, and also one of the key modes of transmission is via the hands of health-care personnel and patients,” said Dr. Lennox Archibald, a professor of infectious diseases at the UF College of Medicine, and the Shands at UF epidemiologist leading the evaluation of HyGreen.

Six pathogens, including the ones known as MRSA and VRE, account for two-thirds of all hospital-acquired infections and are readily transmitted by hand.

Studies have shown that up to half of all hospital-acquired infections might be prevented if health-care workers washed their hands according to guidelines set forth by the CDC.

It costs at least $30 billion a year in additional spending to treat hospital-acquired infections. The Center for Medicare and Medicaid Services last year ruled that it would no longer reimburse hospitals for the expense of treating the infections.

Today, more than 160 years after Hungarian physician Ignaz Semmelweiss was ridiculed for suggesting that hand washing by doctors who moved directly from working with cadavers to delivering babies could reduce fatal cases of birth-related infection, the practice still meets with resistance.

“But it’s not because people don’t want to do it,” Archibald said. “It’s not inherent in people’s behavior to wash their hands, for some reason.”

Various studies show that health-care workers wash their hands less than half the time after direct contact with patients. The reasons people give include skin irritation caused by hand hygiene products, a preference for gloves or simply failure to remember.

Previous hand-washing compliance studies have been based on observation of a limited number of people at a time, who likely improve their behavior when they know they are being watched — a phenomenon known as the Hawthorne effect.

“This system is a noninvasive way of measuring — it allows for nonbiased measurement and is unobtrusive,” said Loretta Fauerbach, Shands at UF director of infection control, who helped write the CDC hand-washing guidelines and leads the collaboration with HyGreen to evaluate the system in a hospital setting.

“Nobody has ever taken a systems approach to this problem before,” said Melker, chief technology officer of Xhale Inc., which is marketing HyGreen.

Developers anticipate that hospitals will readily accept the system because not only can it help reduce infections, it also will pay for itself within a few months.

“Something has to be done about hand washing,” Archibald said. “Otherwise the bugs are going to win.”

Called glycogen storage disease type 1A, the genetic disease stops the body from being able to correctly store and use sugar between meals. In order to survive, children and adults with this disease must receive precise doses of cornstarch every few hours. The disease is even more dire in dogs, which must be fed sugar every 30 minutes to survive.

“Without treatment, these dogs all die,” said Dr. David Weinstein, director of the UF Glycogen Storage Disease Program and co-investigator on the study. “People usually survive because they are fed so much as infants. But by 4 to 6 months of age, they will have developmental delays and a big liver. If it is diagnosed at that point, the kids can do fine. If it is not diagnosed, then the kids get exposed to recurrent low sugars, and they will end up with brain damage, seizures or they will die.”

UF researcher Cathryn Mah, a member of the Powell Gene Therapy Center and UF Genetics Institute, will present the findings at an American Society of Gene Therapy meeting this weekend in San Diego.

About one in 100,000 children have this severe form of glycogen storage disease. Children receive doses of cornstarch at scheduled intervals throughout the day because it metabolizes more slowly than other carbohydrates. Until this therapy was discovered about 30 years ago, most children born with this disease did not survive past infancy.

Glycogen storage disease type 1A stems from a faulty enzyme that doesn’t convert stored sugar, or glycogen, to glucose, the type of sugar the body uses for energy. This prevents the body from getting the energy it needs and causes glycogen to build up in the liver.

The goal of gene therapy is to restore the faulty enzyme so the body uses sugar properly, said Mah, a UF assistant professor of pediatric cellular and molecular therapy and a co-investigator on the study.

The dog, which comes from a line of dogs genetically prone to the disease, received its first dose of gene therapy the day after it was born, Mah said. The dog improved at first, often going as long as two to three hours without needing additional glucose to supplement its diet. But several weeks later the progress stopped.

When the dog was 5 months old, the researchers administered another dose of gene therapy, this time using a different type of AAV. Six weeks after the therapy, the dog was completely weaned off glucose supplements.

“We have never had to use any glucose supplementation since we weaned her off,” Mah said. “She just gets fed normal dog food. That is a huge improvement in quality of life.”

A few years ago, when Weinstein, Mah and other UF and National Institutes of Health collaborators began discussing the project, the longest a dog with the disease had lived was 28 days. The dog treated at UF is now 20 months old.

“The success is beyond what I would have imagined at this stage,” Weinstein said. “To have a dog off treatment for 14 months that is clinically doing great with outstanding lab results is beyond what I even dreamt about.”

Researchers hope to eventually establish a clinical trial in humans, but for now would like to test gene therapy in dogs again within the next year, Weinstein said.

“This is very exciting work and holds great promise for treatment of the disease in humans,” said Joseph Wolfsdorf, a pediatric endocrinologist at Children’s Hospital Boston and professor of pediatrics at Harvard Medical School who studies glycogen storage disease in children.

Finding better treatments for the glycogen storage disease is crucial because the disorder is still associated with multiple complications, and care remains a challenge. As a result of the lack of expertise in this condition, children and adults also must travel to special centers for care. With more than 300 patients from 18 countries, UF’s Glycogen Storage Disease Program is the largest in the world.

Aside from Weinstein and Mah, other collaborators include Catherine Correia and Laurie Fiske, research coordinators for the UF Glycogen Storage Disease Program; John Verstegen, of the UF College of Veterinary Medicine; Thomas Conlon, associate director of the Powell Gene Therapy Toxicology Core; Travis Cossette; Sean Germain; Andrew Specht, of the UF College of Veterinary Medicine; Maggie Struck and Harvey Ramirez, of UF Animal Care Services; Karine Onclin-Verstegen, of the UF College of Veterinary Medicine; Stacy Porvasnik, of the UF College of Medicine; Darin Falk, of the UF College of Medicine; Janice Y. Chou, of the National Institutes of Health; and Dr. Barry J. Byrne, director of the Powell Gene Therapy Center.

The study was funded by the Children’s Fund for Glycogen Storage Disease Research.

In the largest study of its kind, researchers found that in diseased cells — such as cancer cells — that are also infected with HIV, almost all the virus was packed into macrophages, whose job is to “eat” invading disease agents.

What’s more, up to half of the virus in those macrophages were hybrids, formed when pieces of genetic material from several parent HIV viruses combined to form new strains. Such “recombination” is responsible for formation of mutants that easily elude immune system surveillance and escape from anti-HIV drugs.

“Macrophages are these little factories producing new hybrid particles of the virus, making the virus probably even more aggressive over time,” said study co-author Marco Salemi, an assistant professor in the department of pathology, immunology and laboratory medicine at the UF College of Medicine. “If we want to eradicate HIV we need to find a way to actually target the virus specifically infecting the macrophages.”

The work was published recently in the journal PLoS ONE.

At least 1.1 million people in the United States and 33 million in the world are living with HIV/AIDS, according to the Kaiser Family Foundation.

The researchers set out to see if HIV populations that infect abnormal tissues are different from those that infect normal ones, and whether particular strains are associated with certain types of illness.

They tackled the question using frozen post-autopsy tissue samples, pathology results and advanced computational techniques. They analyzed 780 HIV sequences from 53 normal and abnormal tissues from seven patients who had died between 1995 and 2003 from various AIDS-related conditions, including HIV-associated dementia, non-Hodgkin’s lymphoma and generalized infections throughout the body. Four patients had been treated with highly active antiretroviral therapy, called HAART, at or near the time of death.

The researchers compared brain and lymphoma tissues, which had heavy concentrations of macrophages, with lymphoid tissues — such as from the spleen and lymph nodes — that had a mix of HIV-infected macrophages and T cells.

The analyses revealed great diversity in the HIV strains present, with different tissues having hybrid viruses made up of slightly different sets of genes. A high frequency of such recombinant viruses was also found in tissues generally associated with disease processes, such as the meninges, spleen and lymph nodes. The researchers concluded that HIV-infected macrophages might be implicated in tumor-producing mechanisms.

The higher frequency of recombinant virus in diseased tissues likely is because macrophages multiply as a result of an inflammatory response, the researchers said.

“The study points to macrophages as a site of recombination in active disease,” said neurobiologist Kenneth C. Williams, a Boston College associate professor and AIDS expert who was not involved in the study. “So people can say this is one spot where these viruses come from.”

T cells — the so-called conductors of the immune system orchestra, whose decline is the hallmark of HIV disease — are an obvious target for HIV drug development because they die soon after infection, and are readily sampled from the blood and cultured. But although current drugs are effective at blocking infection of new cells and lowering viral loads to barely detectable levels, they never reduce the viral level in an infected person to zero.

“Where is it coming from?” said Michael S. McGrath, the University of California, San Francisco, professor who led the research team. “We believe it’s coming from these macrophages.”

Macrophages, like T cells, can be infected multiple times by HIV. But unlike T cells, when they get infected, they don’t die within days, but live for several months, all the while being re-infected with multiple viruses of different genetic makeup. That situation is ripe for the emergence of hybrids.

“Most people who look at viral sequences assume that evolution of the virus is linear. In the real world that doesn’t happen — large parts of the virus are swapped in and out. This group has shown that in this model,” Williams said. “It sort of overturns the old way of trying to match virus sequence with pathology.”

McGrath’s group is now developing macrophage-targeting drugs that, through a grant from the National Institute of Mental Health, should be in human clinical trials in a few years.

“This is one of the last frontiers — killing off what we believe is a so far untouched reservoir,” he said.

Researchers at the Powell Gene Therapy Center at the University of Florida have discovered that signals from the brain to the diaphragm — the muscle that controls breathing — are too weak to initiate healthy respiration in mouse models of the disease.

The discovery for the first time shifts responsibility to the nervous system for the severe breathing problems experienced by infants with Pompe disease, a rare genetic disorder that causes extreme muscle weakness. Children born with the disorder usually die before age 2.

“For years what we have thought is principally a muscle disease may actually be caused by problems with signaling between the spinal cord and the muscle,” said Dr. Barry Byrne, a UF pediatric cardiologist, a member of the UF Genetics Institute and the director of the Powell Gene Therapy Center. “As we’ve treated children with this disease, we found many of them have become ventilator-dependent, so we went back to the laboratory and found that a significant part of the respiratory deficit is in the spinal cord and not in the diaphragm alone.”

The findings, which will be published the week of May 25 in the online early edition of the Proceedings of the National Academy of Sciences, also have a bearing on motor neuron diseases, a group of incurable brain disorders that destroy cells that influence essential muscle activity such as speaking, walking, breathing and swallowing. Notable among these is ALS, technically known as amyotrophic lateral sclerosis or, more commonly, Lou Gehrig’s disease.

Although many laboratory discoveries never advance to the point where they can be confirmed in patients, scientists will be able to evaluate whether there is indeed a neural aspect to Pompe disease in a clinical safety study of a gene therapy in six infants with the disorder.

The clinical trial, which will begin this summer at UF, had previously advanced on its merits as a therapy for breathing problems in a group of patients who have very few treatment alternatives.

Children with Pompe disease cannot produce the enzyme acid alpha-glucosidase, or GAA. Without the enzyme, sugars and starches that are stored in the body as glycogen accumulate and destroy muscle cells, particularly those of the heart and respiratory muscles.

In this first-in-humans gene therapy for neuromuscular disease, scientists will incorporate the correct gene to produce GAA into an adeno-associated virus, which already exists in most people, and inject it into each patient’s diaphragm. The intent is to “infect” cells of Pompe patients with the genetic machinery they have been missing since birth.

Now, in addition to testing the safety of the dosage and watching closely for signs of therapeutic effects, researchers will fortuitously be able to study the response of the phrenic nerve, which shuttles impulses from the brain to the diaphragm via the spinal cord.

In the PNAS study, UF researchers examined breathing in mice with a form of Pompe disease and in a line of mice genetically engineered to produce GAA only in muscle, not in the central nervous system. In both models, phrenic nerve bursts to stimulate breathing were substantially weaker than in normal mice. As a backdrop, they considered a detailed analysis of a Pompe disease patient’s nervous system, finding similar unhealthy glycogen buildup in the spinal cord and deficient neural output to the diaphragm.

“Treatments that target muscle alone may be ineffective,” Byrne said. “Fortunately the gene transfer we are attempting also affects the phrenic nerve, and we know in mice we can restore phrenic nerve stimulation of the diaphragm. Ultimately we hope that by restoring the function of this gene in both muscle and nerve the patients may have improved respiratory function and possibly breathe independently.”

In addition to Pompe disease, this finding has relevance for congenital and other forms of muscular dystrophy, according to Xiao Xiao, a distinguished professor of gene therapy at the University of North Carolina Eshelman School of Pharmacy at Chapel Hill who was not involved in the research.

“People did not realize there was nerve involvement in these diseases until this study,” Xiao said. “It provides us with a new target for therapy, but it also gives us a new challenge. Not only do we have to deliver to therapy to the muscle and heart, we now have to deliver it to the nerve. Fortunately Dr. Byrne is very well-qualified and positioned to take this therapy from the bench to the bedside.”

The general therapy for children with Pompe disease involves intravenous infusions to replace the missing GAA enzyme, according to Dr. Robert D. Steiner, a professor of pediatrics and molecular and medical genetics and vice chair for pediatric research at Oregon Health & Science University and OHSU Doernbecher Children’s Hospital. In a subset of patients, the enzyme replacement therapy helps initially, but becomes ineffective over time.

“I think this study begins to explain some of the difficulties we’ve had in treating patients,” said Steiner, who did not participate in the research. “The findings are clear that central nervous system involvement is likely to be important in Pompe disease, and that treatments that do not take this into account will not be 100 percent effective in the long-term. It is very reasonable to pursue gene therapy for treatment of this disease, because gene therapy makes it possible to target the central nervous system.”

Other members of the UF research team include Cathryn Mah, an assistant professor of pediatrics, and Paul Reier, a professor of neuroscience, both in the College of Medicine; and David Fuller, an assistant professor of physical therapy in the College of Public Health and Health Professions. The research was funded by the National Institutes of Health.

In findings to be published this week in the online early edition of the Proceedings of the National Academy of Sciences, scientists describe how they looked at all of the proteins produced by the smallpox virus in concert with human proteins, and discovered one particular interaction that disables one of the body’s first responders to injury — inflammation.

“This virus that has killed more humans than any other contains secrets about how the human immune system works,” said Grant McFadden, a professor of molecular genetics and microbiology at the College of Medicine and a member of the UF Genetics Institute. “I’m always amazed at how sophisticated these pathogens are, and every time we look, they have something new to teach us about the human immune system.”

With researchers from the University of Alberta, the Centers for Disease Control and Prevention and a private company called Myriad Genetics, UF researchers for the first time systematically screened the smallpox proteome — the entire complement of new proteins produced by the virus — during interactions with proteins from human DNA.

These protein-on-protein interactions resulted in a particularly devastating pairing between a viral protein called G1R and a human protein called human nuclear factor kappa-B1, which is believed to play a role in the growth and survival of both healthy cells and cancer cells by activating genes involved in immune responses and inflammation.

“One of the strategies of the virus is to inhibit inflammation pathways, and this interaction is an inhibitor of human inflammation such that we have never seen before,” McFadden said. “This helps explain some of the mechanisms that contribute to smallpox pathogenesis. But another side of this is that inflammation can sometimes be harmful or deadly to people, and we may learn a way to inhibit more dangerous inflammation from this virus.”

Smallpox is blamed for an estimated 300 million deaths in the 20th century alone, and outbreaks have occurred almost continuously for thousands of years. The disease was eradicated by a worldwide vaccination campaign, and the last case of smallpox in the United States was in 1949, according to the CDC. The last naturally occurring case in the world was in Somalia in 1977.

With the exception of stores of the virus held in high-containment facilities in the United States and Russia, smallpox no longer exists on the planet. Since it was no longer necessary for prevention, and because the vaccines themselves were risky, routine vaccination against smallpox was stopped. However, public health concerns regarding the possible re-emergence of the virus through bioterrorism have led to renewed interest in the development of treatments for the disease and safer vaccines.