TAG: "Infectious disease"

Making maps to predict malaria


UCSF, Google Earth Engine fighting infectious disease with cloud computing.

A sample risk map of malaria in Swaziland during the transmission season using data from 2011-13.

UC San Francisco (UCSF) is working to create an online platform that health workers around the world can use to predict where malaria is likely to be transmitted using data on Google Earth Engine.

The goal is to enable resource poor countries to wage more targeted and effective campaigns against the mosquito-borne disease, which kills 600,000 people a year, most of them children.

Faced with a multitude of public health needs, countries often make the mistake of cutting their malaria efforts just when they are close to eliminating the disease, said Hugh Sturrock, Ph.D., M.Sc., an assistant professor of epidemiology and biostatistics and a researcher in the Global Health Group, which is a part of UCSF’s Global Health Sciences.

“This can have disastrous consequences, since malaria can quickly rebound, putting years of expensive control efforts to waste,” he said. “But with these maps, health workers will know exactly where to target their scarce resources. That way, they can keep fighting the disease until it’s eliminated within their borders.”

Google Earth Engine brings together the world’s satellite imagery — trillions of scientific measurements dating back almost 40 years — and makes it available online with tools for scientists, independent researchers and nations to mine this massive warehouse of data to detect changes, map trends and quantify differences on the Earth’s surface.

With the malaria prediction platform, local health workers will be able to upload their own data on where and when malaria cases have been occurring and combine it with real-time satellite data on weather and other environmental conditions within Earth Engine to pinpoint where new cases are most likely to occur. That way, they can spray insecticide, distribute bed nets or give antimalarial drugs just to the people who still need them, instead of blanketing the entire country.

By looking at the relationship between disease occurrence and factors such as rainfall, vegetation and the presence of water in the environment, the maps will also help health workers and scientists study what drives malaria transmission. Google Earth Outreach, which helps nonprofits use Google’s mapping technology, is giving UCSF $100,000 to develop the new platform.

The new tool will be piloted in Swaziland, a country in southern Africa that has limited malaria to a few small pockets across the country through the malaria elimination program it launched in 2008 with help from the Global Health Group. Plans are to make the tool available to health workers in other countries working with the Global Health Group’s Malaria Elimination Initiative. The tool could also be adapted to predict other infectious diseases.

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Researchers assisting in search for Ebola immune response targets


San Diego Supercomputer Center, La Jolla Institute provide rapid online analysis.

The effort to develop therapeutics and a vaccine against the deadly Ebola virus disease (EVD) requires a complex understanding of the microorganism and its relationship within the host, especially the immune response. Adding to the challenge, EVD can be caused by any one of five known species within the genus Ebolavirus (EBOV), in the Filovirus family.

Now, researchers at the La Jolla Institute for Allergy and Immunology (La Jolla Institute) and the San Diego Supercomputer Center (SDSC) at UC San Diego are assisting the scientific community by running high-speed online publications of analysis of EBOV-related epitope data being curated in the Immune Epitope Data Base (IEDB), and predicting epitopes using the IEDB Analysis Resource. Sebastian Maurer-Stroh of Bioinformatics Institute, A*STAR, Singapore is also assisting with analysis of the latest outbreak sequences of Ebola proteins.

“These results are the first installment of a series of analysis, whose ultimate goal is to provide a comprehensive overview of the molecular targets of the immune responses to Ebola virus,” said Julia Ponomarenko, a senior research scientist at SDSC and UCSD PI of IEDB.

The recent Ebola outbreak in West Africa has now reached historic proportions surpassing 1,900 deaths from 3,500 confirmed or probable cases, prompting the World Health Organization (WHO) to declare an international public health emergency, according to recent news reports. Outbreaks of EVD have occurred in Africa in the past; however the current epidemic, caused by Zaire Ebolavirus, has been characterized by its unprecedented breadth and rapid spread.

“Clearly, research related to development of therapeutics and a vaccine against EVD is an urgent need, as well-engineered vaccines don’t exist at this time; our analysis is aimed at assisting the clinical and scientific communities in fine evaluation of laboratory results with the express intent of improving therapeutic targets or new vaccine development,” said Alessandro Sette of the Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, IEDB PI.

As of last month, the IEDB reported, in preliminary analysis, 67 T cell (CD4+ and CD8+) and 35 B cell epitopes (linear and conformational), from viruses within the EBOV and Marburgvirus genera. Within EBOV, data are provided for all known species, including Zaire, Sudan, Reston, Bundibugyo, and Tai Forest Ebolavirus. To date, 29 papers have been published that describe experimental data on the epitopes in the Filoviridae family, with 23 papers focused on the EBOV-related epitope data.

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Diaper detective


Students develop inexpensive, versatile pad to detect medical problems in infants.

A team of UC Riverside Bourns College of Engineering students created an inexpensive pad that can be inserted into diapers to detect dehydration and bacterial infections in infants.

The product, which recently won an award that included a $10,000 prize at a national engineering design contest, operates much like a home pregnancy test or urine test strip. Chemical indicators change color when they come in contact with urine from an infant who is suffering from dehydration or a bacterial infection.

The pad, which is 2.5 inches by 5 inches and called “The Diaper Detective,” is attractive for numerous reasons. It costs 34 cents to make. It doesn’t require electricity, cold storage or an advanced education to interpret. It’s customizable so that other chemical indicators can be added to test for other medical conditions. And it could be adapted to be used in adult diapers.

“We created this to fulfill a need for a versatile, inexpensive, non-invasive method of urine collection in developing countries and elsewhere,” said Veronica Boulos, one of the team members. “The beauty of this is that it solves a huge problem with simplicity.”

Strike against infant mortality

The Diaper Detective addresses the worldwide problem of infant mortality in developing nations. Of the estimated 3.9 million annual neonatal deaths, 98 percent occur in developing countries and could be prevented with access to low cost, point-of-care diagnostics.

In developing countries, the students hope the Diaper Detective will be distributed via relief organizations. In the United States, the students believe the pad would qualify for reimbursement through medical insurance, making it an inexpensive option for low-income users.

The uniqueness of the diaper insert comes from the use of lateral flow channels that guide the user’s urine to the reactive regions where the color change takes place. The lateral flow channels were originally created using Crayola crayons and are now created by paraffin wax and a laser printer.

The students won a third place award at the National Institute of Biomedical Imaging and Engineering Design by Biomedical Undergraduate Teams Challenge. They have also submitted the product to the National Collegiate Inventors and Innovators Alliance BMEStart competition.

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Infants receiving different diets after birth develop distinct immune systems


Study compares breast- and bottle-fed infant monkeys.

Researchers have long known that breast milk is good for babies. This research gives further insight about why that might be so and suggests immunologic effects may persist long after breast feeding has ceased. (Photo by Kathy West, California National Primate Research Center)

Infant rhesus monkeys receiving different diets early in life develop distinct immune systems that persist months after weaning, a study by researchers from UC Davis, the California National Primate Research Center (CNPRC) at UC Davis and UC San Francisco has shown. The study, which compares breast- and bottle-fed infants, appears online today (Sept. 3) in Science Translational Medicine.

While the researchers expected different diets would promote different intestinal bacteria (microbiota), they were surprised at how dramatically these microbes shaped immunologic development. Specifically, breast-fed macaques had more “memory” T cells and T helper 17 (TH17) cells, which are known to fight salmonella and other pathogens.

These differences persisted for months after the macaques had been weaned and placed on identical diets, indicating that variations in early diet may have long-lasting effects.

“We saw two different immune systems develop: one in animals fed mother’s milk and another in those fed formula,” said Dennis Hartigan-O’Connor, a CNPRC scientist in the Infectious Diseases Unit and Reproductive Sciences and Regenerative Medicine Unit, and an assistant professor in the Department of Medical Microbiology and Immunology at UC Davis.

“But what’s most startling is the durability of these differences. Infant microbes could leave a long-lasting imprint on immune function,” he said.

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Malaria’s clinical symptoms fade on repeat infections


UCSF-led team finds that this might be in part to loss of immune cells.

Researchers have been studying immune responses to the malaria parasite in Tororo, Uganda, where infection is now more prevalent than Kampala, the Ugandan capital.

Children who repeatedly become infected with malaria often experience no clinical symptoms with these subsequent infections, and a team led by UC San Francisco researchers has discovered that this might be due at least in part to a depletion of specific types of immune cells.

Working in Uganda, one of the most malaria-plagued nations in Africa and one in which individuals are repeatedly exposed to the malaria parasite, UCSF scientists found that a depletion of immune cells known as gamma delta T cells diminishes inflammatory responses in infected children — responses that when unabated can become debilitating or deadly.

“These inflammatory immune cells are depleted in children with repeated malaria exposure, and those that remain behave differently than the same cell types in children who have not previously been infected,” said Prasanna Jagannathan, M.D., an assistant professor of medicine at UCSF, who conducted the lab analysis as part of a study team led by Margaret Feeney, M.D., a UCSF professor of experimental medicine and pediatrics. The study was published online today (Aug. 27) in the journal Science Translational Medicine.

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Protein ID’d that helps prevent active TB in infected patients


Discovery could help doctors identify people at greatest risk for the disease.

A UCLA-led study has identified a protein that appears to play a key role in protecting people infected with Mycobacterium tuberculosis — the bacterium that causes tuberculosis — from developing the active form of the disease. The protein, interleukin-32, was discovered to be one biomarker of adequate host defense against TB.

The discovery could help doctors identify people who are at the greatest risk for the highly contagious and potentially fatal lung disease, and it could point the way toward new treatment strategies for TB.

The study, conducted in partnership with researchers from Harvard University School of Public Health and the University of Michigan School of Medicine, was published in the Aug. 20 online edition of the journal Science Translational Medicine.

The findings underscore the importance of maintaining sufficient levels of vitamin D to effectively combat the pathogen that causes TB. The researchers found that the protective protein, interleukin-32, can induce the killing of the TB bacterium only in the presence of sufficient levels of vitamin D.

An estimated one-third of the world’s population is infected with tuberculosis, but the disease is latent in 90 to 95 percent of infected people, meaning that they experience no symptoms and are not contagious. Interleukin-32 contributes to maintaining that latent state and preventing active infection. In 2012, nearly 9 million people worldwide became sick with TB and there were 1.3 million TB-related deaths, according to the U.S. Centers for Disease Control and Prevention.

A new urgency for developing new approaches to identify individuals at risk, maintain immunity and treat active disease has arisen in recent years as TB has re-emerged as a global health threat — thanks in part to the rise of extremely drug-resistant bacteria.

“Until now, there had been no way to predict, based on biological factors, why latently infected individuals do not develop active tuberculosis,” said Dennis Montoya, a postdoctoral scholar in the division of dermatology at the David Geffen School of Medicine at UCLA and the study’s lead author. “We were surprised to find many differences between people with latent TB and healthy people, suggesting that people with latent TB may have activated immune systems that are protecting them from developing active infection.”

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New vaccine may be stronger weapon against both TB and leprosy


Research finds variant of existing vaccine offers stronger protection against both diseases.

Antigen 85B structure

In many parts of the world, leprosy and tuberculosis live side-by-side. Worldwide there are approximately 233,000 new cases of leprosy per year, with nearly all of them occurring where tuberculosis is endemic.

The currently available century-old vaccine Bacille Calmette-Guerin, or BCG, provides only partial protection against both tuberculosis and leprosy, so a more potent vaccine is needed to combat both diseases. UCLA-led research may have found a stronger weapon against both diseases.

In a study published in the September issue of the peer-reviewed journal Infection and Immunity, the researchers found that rBCG30, a recombinant variant of BCG that overexpresses a highly abundant 30 kDa protein of the tuberculosis bacterium known as Antigen 85B, is superior to BCG in protecting against tuberculosis in animal models, and also cross protects against leprosy. In addition, they found that boosting rBCG30 with the Antigen 85B protein, a protein also expressed by the leprosy bacillus, provides considerably stronger protection against leprosy.

“This is the first study demonstrating that an improved vaccine against tuberculosis also offers cross-protection against Mycobacterium leprae, the causative agent of leprosy,” said Dr. Marcus A. Horwitz, professor of medicine and microbiology, immunology and molecular genetics, and the study’s senior author. “That means that this vaccine has promise for better protecting against both major diseases at the same time.

“It is also the first study demonstrating that boosting a recombinant BCG vaccine further improves cross-protection against leprosy,” he added.

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Antimalarial drug shipped to Africa


Project begun by Berkeley Lab’s Jay Keasling to benefit millions of people.

Jay Keasling with children in a village outside Nairobi, Kenya. (Photo by Gabrielle Tenenbaum)

A project begun some 13 years ago by Jay Keasling, the associate laboratory director for biosciences at Berkeley Lab and the CEO of the Joint BioEnergy Institute (JBEI), was culminated with an announcement on Aug. 12 from the partnership of Sanofi, the multinational pharmaceutical company, and PATH, the nonprofit global health organization. Sanofi/PATH announced the shipment of 1.7 million treatments of semi-synthetic artemisinin to malaria-endemic countries in Africa. Unlike conventional artemisinin, which is derived from the bark of the sweet wormwood plant, this synthetic version of the World Health Organization’s frontline antimalarial drug is derived from yeast. The addition of a microbial-based source of artemisinin to the botanical source provides a stable new option for treating the millions of victims who are stricken with malaria each year, most of them children.

Sanofi has produced enough of the drug for 70 million treatments, and has the capacity to produce up to 150 million treatments annually. It was Keasling and his research group, using the tools of synthetic biology, who engineered the genes and metabolic pathways that enabled first E. coli and later yeast to produce artemisinic acid, the precursor to artemisin. This led to a $42.6 million grant from the Bill and Melinda Gates Foundation for further basic research that ultimately led to yesterday’s announcement by Sanofi/PATH. Keasling, who is also the Hubbard Howe Jr. Distinguished Professor in Biochemical Engineering at UC Berkeley, among other titles, has been recognized for leading this groundbreaking research with numerous awards including the Biotechnology Industry Organization’s first Biotech Humanitarian Award.

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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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