TAG: "Infectious disease"

Grant will advance research on African malaria mosquito

UC Riverside’s Bradley White will produce critical tool aimed at crippling Anopheles gambiae.

Bradley White, UC Riverside

Malaria, the most deadly mosquito-borne disease, kills more than 500,000 people each year, with more than 90 percent of the deaths occurring in sub-Saharan Africa.  While poverty and poor medical care contribute to the African malaria burden, the importance of the uniquely efficient mosquito vectors present in Africa cannot be overlooked.

One particularly promising area of research involves genetic engineering of mosquitoes to prevent transmission.  Although great progress has been made in developing mosquitoes that cannot transmit malaria, more knowledge is needed before such mosquitoes can be released.

Bradley White, an assistant professor of entomology at UC Riverside, has received a five-year grant of more than $1.8 million from the National Institute of Allergy and Infectious Diseases, one of the many institutes that make up the National Institutes of Health (NIH). The grant will allow his lab to produce fine-scale recombination rate maps for the African malaria mosquito, Anopheles gambiae.

The grant is a NIH “R01” grant, RO1 being an NIH activity code.  At 31, White is one of the youngest NIH R01 principal investigators in the country (well less than 1 percent of NIH principal investigators are 31 or younger).

“By the end of the project, we will have produced these recombination rate maps that can be used to model and predict the efficacy of various novel vector control strategies,” said White, who joined UC Riverside in 2011.  “Ultimately, this project will provide a critical tool in the ongoing fight against one of humanity’s ancient foes.”

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A key step toward a safer strep vaccine

UC San Diego gene discovery identifies molecular pathway to potential preventive treatment.

Electron micrograph, false color, of group A Streptococcus bacteria

An international team of scientists, led by researchers at the UC San Diego School of Medicine, have identified the genes encoding a molecule that famously defines Group A Streptococcus (strep), a pathogenic bacterial species responsible for more than 700 million infections worldwide each year.

The findings, published online in today’s (June 11) issue of Cell Host & Microbe, shed new light on how strep bacteria resists the human immune system and provides a new strategy for developing a safe and broadly effective vaccine against strep throat, necrotizing fasciitis (flesh-eating disease) and rheumatic heart disease.

“Most people experience one or more painful strep throat infections as a child or young adult,” said senior author Victor Nizet, M.D., professor of pediatrics and pharmacy. “Developing a broadly effective and safe strep vaccine could prevent this suffering and reduce lost time and productivity at school and work, estimated to cost $2 billion annually.”

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Just-in-time diagnosis

UCSF uses advanced DNA sequencing technology to diagnose infection, save critically ill boy.

Joshua Osborn, 15, flips on the trampoline in the backyard of his home in Cottage Grove, Wis., on May 31. (Photo by John Maniaci)

A mysterious ailment sent an active teenage boy into a medically induced coma, and no one could figure out the cause.

As precious time passed, a team at UC San Francisco employed advanced DNA sequencing technology to find a needle-in-the-haystack answer. What they found led them to a life-saving, and surprisingly simple, treatment.

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Faster DNA sleuthing saves critically ill boy

UCSF genome experts show value of ‘next-generation sequencing’ in diagnosing infection.

Charles Chiu, UC San Francisco

A 14-year-old boy’s turnaround and quick recovery after mysteriously being stricken by brain-inflaming encephalitis – which led to him being hospitalized for six weeks and put into a medically induced coma after falling critically ill – shows that the newest generation of DNA analysis tools can be harnessed to reveal the cause of a life-threatening infection even when physicians have no suspects.

The quick diagnosis and successful treatment of the adolescent just 48 hours after cerebrospinal spinal fluid and blood were received for analysis portends the broader application of powerful, “next-generation sequencing” (NGS) techniques in solving infectious disease mysteries, not only in cutting-edge research labs, but also in clinical laboratories accessible to hospital physicians everywhere, according to Charles Chiu, M.D., Ph.D., a professor of laboratory medicine at UC San Francisco. Chiu is senior author of the case study, published online in the New England Journal of Medicine (NEJM) today (June 4).

The workflow pipeline developed in Chiu’s UCSF laboratory to streamline genetic sleuthing of disease pathogens with NGS dramatically cut the time between sample collection and actionable diagnosis and helped a medical team at the University of Wisconsin save the young patient’s life.

The NEJM study reflects the convergence of faster DNA sequencing, ever-growing genome databases for identifying pathogens and other organisms, and more sophisticated computational analysis tools to quickly analyze millions of data points. The protocol enabled rapid sequencing and simultaneous identification of all DNA in the patient samples without culturing or targeting for specific infectious disease agents.

“From the perspective of cost and turnaround time, this is a very powerful technology that has become practical to implement routinely in clinical laboratories,” Chiu said. Some clinical labs now offer NGS testing to identify cancer mutations in clinical trials and to identify mutations underlying birth defects, but until now NGS has been regarded as too slow and laborious to be useful for routine infectious disease diagnosis.

Study co-author Joseph DeRisi, Ph.D., chair of biochemistry and biophysics at UCSF, a Howard Hughes Medical Institute (HHMI) investigator, and a leader in using new genomics techniques to identify previously unknown pathogens, such as the SARS coronavirus, said that at a cost of a few thousand dollars, essentially any pathogen now can be detected with a single test.

“This is one test to rule them all,” DeRisi said.

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Research targets three neglected tropical diseases

UC, partner researchers receive $6M to target Chagas’ disease, dengue, onchocerciasis.

Researchers at UC San Francisco, UC Berkeley and partner institutions are receiving $6 million to speed development of new tools and technologies that will address three neglected tropical diseases that place a huge health and economic burden on people in Central and South America: Chagas’ disease, dengue and onchocerciasis.

Led by scientists at UCSF Global Health Sciences and funded jointly by the Bill & Melinda Gates Foundation and the Instituto Carlos Slim de la Salud (the Carlos Slim Health Institute), the two-year project is titled FIRST (Fighting Infections through Research, Science, and Technology). The research, which is already under way, will focus on Mesoamerica, which comprises the Southern states of Mexico and Central America from Guatemala to Panama. A significant number of people, mainly of indigenous descent, live in poverty in these countries, making them vulnerable to illness and death.

FIRST promises to address three diseases that collectively affect billions of people worldwide, and have significant health and economic effects, by helping to find better treatments, more effective vaccines and other ways to prevent them.

“We are selecting projects that will give us quick wins, allowing us to make a huge impact immediately, as well as game-changing, high-risk research that will make a significant impact in the long term,” said Jaime Sepulveda, M.D., M.P.H., M.Sc., Dr.Sc., the executive director of UCSF Global Health Sciences.

“Although transmission of onchocerciasis has been interrupted in Mesoamerica, many indigenous communities are still at high-risk because current treatments do not kill the adult worms,” said Jim McKerrow, the principal investigator on the onchocerciasis project and a UCSF professor of pathology. “We will carry out a clinical trial with collaborators in Cameroon and the UK to determine whether Auranofin, an FDA approved drug, can be repurposed as a macrofilaricide to kill adult worms.”

The aims of the other projects in the FIRST portfolio include developing:

  • Low-cost diagnostic tools for early detection of dengue
  • Information systems that will provide early warnings of dengue outbreaks
  • New tests to guide dengue vaccine development
  • A cell phone app for crowdsourcing mosquito control
  • New, less toxic drugs for Chagas’ disease
  • Better biomarkers to monitor treatment of Chagas’ disease.

In addition to UCSF, researchers whose work will be funded by this project are affiliated with Blood Systems Research Institute, Liverpool School of Tropical Medicine, Sustainable Sciences Institute in San Francisco and Nicaragua, UC Berkeley, UC San Diego, UC Santa Cruz, University of North Carolina, and University of Sao Paulo.

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Why dengue fever prevention efforts often fail

Twelve-year study provides insights.

Studies on dengue fever infections took UC Davis researcher Robert Reiner (foreground) to Iquitos, Peru.

Newly published research involving a 12-year study of dengue infections in Iquitos, Peru, helps explain why interventions to prevent the mosquito-borne disease are frequently unsuccessful.

The research, headed by professor Thomas Scott of the UC Davis Department of Entomology and Nematology, is published today (May 19) in the Proceedings of the National Academy of Sciences.

“Defining variation in the risk of dengue transmission has been a roadblock to understanding disease dynamics and designing more realistic and effective disease prevention programs,” said Scott, a noted dengue researcher and a senior author of the paper, “Time-Varying, Serotype-Specific Force of Infection of Dengue Virus.”

“This study is an important step toward overcoming that obstacle,” Scott said. “We hope our results will help reduce the burden of this increasingly devastating disease.”

Dengue, a mosquito-borne virus infecting nearly 400 million people a year, is difficult to model not only because the majority of all infections are hidden, but also because there are four distinct serotypes, or versions, of dengue, each having unique characteristics, said lead author Robert Reiner, a Research and Policy for Infectious Disease Dynamics (RAPIDD) postdoctoral fellow in Scott’s Mosquito Research Laboratory.

“Typically, most infections go unnoticed and as such, measuring and modeling transmission intensity is problematic,” Reiner said.

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UC Davis Children’s Hospital opens recurrent MRSA clinic

Clinic will be accepting referrals from primary care physicians.

Pediatric patients with recurrent MRSA (methicillin-resistant Staphylococcus aureus) can find the help they seek at UC Davis Children’s Hospital’s new clinic.

The Recurrent MRSA Clinic will open Tuesday, May 6, and will be accepting referrals from primary care physicians.

Dean Blumberg, chief of pediatric infectious diseases at UC Davis, has been caring for patients with MRSA for over a decade and has seen an increase in cases over the past five years. He has developed a tried-and-tested line of defense to help treat and prevent future outbreaks.

“I see the frustration that families face every day when battling community-associated MRSA. I developed this clinic to provide parents with the right resources to fight it once and for all, so they can get back to their day-to-day lives,” said Blumberg.

Blumberg has been able to reduce MRSA recurrences, if not eliminate them, in more than 95 percent of his pediatric patients. In most cases, no further MRSA infections occur after one clinic visit.

According to the U.S. Centers for Disease Control and Prevention, two in 100 people carry MRSA. MRSA is a bacteria that is resistant to many antibiotics. People can transmit MRSA through direct contact with an infected wound or by sharing personal items, such as towels or razors, that have touched someone’s infection. MRSA is frequently spread in places that involve crowding, skin-to-skin contact, and shared equipment or supplies. Most community-associated MRSA infections are skin infections.

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Declines in large wildlife lead to increases in disease risk

Research shows biodiversity loss heightens risk of animal-to-human disease transmission.

A plains zebra in front of the Kenya Long-Term Exclosure experiment.

In the Middle Ages, fleas carried by rats were responsible for spreading the Black Plague. Today in East Africa, they remain important vectors of plague and many other diseases, including Bartonellosis, a potentially dangerous human pathogen.

Research by Hillary Young, assistant professor in UC Santa Barbara’s Department of Ecology, Evolution and Marine Biology, directly links large wildlife decline to an increased risk of human disease via changes in rodent populations. The findings appear today (April 28) in the Proceedings of the National Academy of Sciences Early Online Edition.

With an East African savanna ecosystem as their research site, Young and her colleagues examined the relationship between the loss of large wildlife — defaunation — and the risk of human disease. In this case, they analyzed Bartonellosis, a group of bacterial pathogens which can cause endocarditis, spleen and liver damage and memory loss.

“We were able to demonstrate that declines in large wildlife can cause an increase in the risk for diseases that are spread between animals and humans,” said Young. “This spike in disease risk results from explosions in the number of rodents that benefit from the removal of the larger animals.”

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Sen. Boxer praises UC efforts to prevent medical errors

She tours UCLA, notes its safety measures.

Sen. Barbara Boxer observes two nurses demonstrating a bar code scanning safety procedure at Ronald Reagan UCLA Medical Center.

Every year, 325,000 patients die in the United States due to medical errors, a number that would fill the Rose Bowl nearly four times, according to a special report released today (April 25) at a UCLA news conference by U.S. Sen. Barbara Boxer (D-Calif.).

Boxer presented the findings of her report at Ronald Reagan UCLA Medical Center and noted steps UCLA already takes to prevent medical errors and that could serve as models for other hospitals around the country. Boxer’s report also highlighted efforts by UC Davis to reduce ventilator-associated pneumonia and by UC San Diego to reduce blood clots and central line bloodstream infections.

“These deaths are all the more heartbreaking because they’re preventable,” Boxer said after she toured the medical center with Dr. David Feinberg, president and chief executive officer of the UCLA Health System, so she could see for herself two systems being used to prevent medical errors. “This is not the time to sit back and do nothing. I will not turn away from this challenge when I have the opportunity to pull back 325,000 people from disaster every year simply by preventing medical errors.”

The third leading cause of death in the country, medical errors can be avoided by something as simple as washing your hands. These errors commonly result in hospital-acquired infections, bedsores, patient falls, adverse drug reactions, sepsis, blood clots, catheter-related urinary tract infections, ventilator-related pneumonias and surgical site infections. In addition to saving lives, preventing medical errors could save up to $19.5 billion annually, Boxer said.

While touring the seventh floor, Boxer was first was shown the bar code technology and electronic medical records system used at UCLA to ensure patients receive the right medications in the right doses at the correct times. The process begins with a medication dispenser that operates much like a vending machine, providing one dose of drug at a time. A nurse logs in to the patient’s medical record to determine what medications are due and accesses them from the dispenser.

Once in the patient’s room, a nurse logs into a bedside computer and scans a bar code on the patient’s armband that automatically opens up his or her electronic medical record. The nurse then scans the medication, which is individually wrapped and bar-coded for that specific patient. If the medication’s bar code isn’t recognized as belonging to the patient’s medication profile, a warning will flash on the computer screen. After giving the patient the medication, the nurse selects the “administer” button, which instantly updates the medical record that the medication has been administered.

UCLA nurses were heavily involved the development of the bar code system, said Renee Appleby, director for the seven west cardiothoracic telemetry unit. The nurses first studied the errors to determine what was going wrong, and then participated in the creation of a safer system.

Boxer called the bar code and electronic medical record system “exciting, an enormous change for the better,” and said it must give the UCLA medical team more peace of mind.

“As a nurse, it makes me feel safe,” nurse Megan Kelly told Boxer.

Prior to the installation of the bar code system, the medical center was making two to four medication errors a month. Since the new system has been in place, no medical errors have been made, Appleby said.

That’s an impressive accomplishment, since the medical center dispenses five million doses of medication a year, said Cathy Ward, UCLA’s chief nursing officer.

“You’re really doing everything you can to save lives,” Boxer said. “Congratulations.”

Boxer then went to the seventh floor ICU to see the medical center’s ultraviolet disinfection system in action. The medical center has two Xenex machines, which can disinfect a hospital room in five minutes. The Star Wars-like robots use a Xenon bulb, a powerful form of UV light, combined with technology that generates high intensity pulses of light that are effective against 22 pathogens, including MRSA.

“The light kills micro-organisms by breaking down the cell walls of bacteria and fungus,” said Dr. Daniel Uslan, assistant clinical professor of medicine in the division of infectious disease.

“This is amazing technology that will help save lives,” Boxer said.

Feinberg said he is proud of UCLA’s commitment to patient safety and he looks forward to partnering with Boxer to find new and effective ways to ensure patients remain safe.

The report was compiled after Boxer wrote to 283 California acute care hospitals asking them to respond with the actions they are taking to reduce medical errors. Of those, 149 hospitals responded.

All of hospitals that responded reported taking at least some steps to address the most common medical errors, Boxer said. The report includes some common approaches to combating medical errors, such as using bar code technology and electronic health records to ensure patients receive proper medications to avoid adverse drug events. This technology is currently in use at Ronald Reagan UCLA Medical Center.

Other common approaches to preventing medical errors in the report included maintaining hand hygiene, using central line anti-microbial port covers, assessing all patients for bedsores prior to and upon admission, assessing patients for blood clot risks preoperatively and elevating the heads of patients on ventilators from 30 to 45 degrees.

Boxer’s report, which will be sent to the 283 hospitals initially queried, made six recommendations to improve patient safety, including:

  • Requiring all federal programs designed to reduce medical errors to work off a single list where appropriate, specifically the Partnership for Prevention’s list of the nine most common medical errors.
  • Having the Department of Health and Human Services report to Congress the time it takes for quality measures to be developed, endorsed and implemented in programs related to medical error reduction.
  • Creating a standard way of reporting medical errors, allowing hospitals and researchers to better collect data on errors, their frequency and where they are occurring.
  • Evaluation of information collected by hospitals when assessing whether medical centers are meeting the requirement to track and report adverse events as a condition of participation in Medicare.
  • Have Congress review the adequacy of whistleblower protections to ensure health care providers are able to report errors.
  • Have the Office of the Inspector General examine the Hospital Patient Safety Initiative’s new surveyor tools and analyze their impact on increasing staff reporting of medical errors.

“If we work together, we can prevent these needless tragedies,” the report states. “If we ensure that doctors, nurses, hospital administrators, medical technology leaders, federal officials and patient advocates are all focused on this common goal, we can make great progress in preventing avoidable deaths and ending the epidemic of medical errors in this country.”

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UCSF joins research partnership to eliminate malaria in Namibia

University’s work already has contributed to 98 percent drop in malaria cases in Namibia.

As we mark World Malaria Day this year, UC San Francisco’s Global Health Group is celebrating the success of Namibia, where malaria case have dropped 98 percent over the past decade.

In 2003, Namibia saw 450,000 cases of malaria; in 2013, that number fell to 2,500. The country is now on track to becoming malaria-free by 2020.

The deadly disease, caused by parasites that are transmitted from person to person by mosquitoes, is now found mostly in the northern regions of Namibia.

The National Vector-borne Disease Control Program (NVDCP) at the Namibia Ministry of Health and Social Services effectively controls the spread of malaria with interventions such as spraying dwellings with insecticides, distributing mosquito nets treated with insecticides, using malaria tests that can give accurate results within 15 minutes, and distributing medicines that kill the parasite.

To further this success, the UCSF Global Health Group’s Malaria Elimination Initiative is teaming up with the Multidisciplinary Research Centre at the University of Namibia, the Novartis Foundation for Sustainable Development, the London School of Hygiene and Tropical Medicine, the Clinton Health Access Initiative, and others to research new strategies and interventions that the NVDCP can use to get rid of the remaining pockets of transmission and eliminate malaria by 2020. Members of this research partnership will be working together to strengthen the national malaria surveillance system, learn more about how to eliminate the remaining reservoirs of infection in the Zambezi region and understand the risk factors that are associated with malaria transmission.

Worldwide, an estimated 3.3 million lives have been saved since 2000 through stepped up malaria control and elimination efforts, according to the World Health Organization. Mortality rates have been cut almost in half.

UCSF’s Global Health Group received a $15 million grant from the Bill & Melinda Gates Foundation in December to help nearly three dozen countries eliminate malaria within their borders.

In 2012, an estimated 207 million people got sick from malaria, and 627,000 of them died, mostly children under five in sub-Saharan Africa. In 2013, 97 countries had ongoing malaria transmission.

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UC Irvine Health-led study earns Top 10 Clinical Research Achievement

MRSA study honored by Clinical Research Forum.

Susan Huang, UC Irvine

A study on antibiotic-resistant bacteria in hospitals led by UC Irvine Health infectious disease expert Dr. Susan Huang earned a “Top 10 Clinical Research Achievement Award” for 2013 from the Clinical Research Forum.

Huang, medical director of epidemiology and infection prevention for UC Irvine Health, is an associate professor of medicine. Winning projects represent the outstanding examples of research projects that benefit the health and well being of the general public.

The study showed that using germ-killing soap and ointment in hospitals on all intensive-care unit patients can reduce bloodstream infections by up to 44 percent and significantly reduce the presence of methicillin-resistant Staphylococcus aureus (MRSA). Patients who have MRSA present on their bodies are at increased risk of developing a MRSA infection and can spread the germ to other patients.

In the study, which was designed to test three MRSA prevention strategies, researchers found that treating all ICU patients with germ-killing soap and ointment was more effective than strategies that relied on screening patients for MRSA first, then applying prevention strategies only to those who carry the germ. This approach was also effective for preventing infections caused by germs other than MRSA. Study results appeared in the New England Journal of Medicine.

“Clinical research culminates years of basic and translational science to bring new treatments to patients, and I’m always excited to see the groundbreaking clinical research recognized every year by the Clinical Research Forum,” said National Institutes of Health Director Francis S. Collins, M.D., Ph.D. “This is just the tip of the iceberg of the incredible work coming out in the field, much of it funded by the NIH.”

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Dr. Elliot Goldstein, former UC Davis infectious diseases chief, dies

He was 79.

Dr. Elliot Goldstein, professor emeritus and former chief of the UC Davis Division of Infectious Diseases, died on March 31, in Woodland.

Dr. Goldstein was born in New York on Dec. 29, 1934, the eldest son of Joseph and Frieda Goldstein. He graduated from Stuyvesant High School and received a bachelor’s degree from Cornell University in 1956 and his medical degree from Cornell Medical College in 1960.

Dr. Goldstein trained at UC San Francisco; Bellevue Hospital, Columbia Division; and Channing Laboratories, Harvard University. He was an instructor at Harvard; a professor and chief of infectious disease at UC Davis; and professor and director of infectious disease at Kansas University Medical College. He was twice selected as a Fulbright research scholar to the Netherlands and lectured around the world.

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