PREDICTABILITY IN THE SPREAD OF DISESE AMONG SPECIES

FROM:  NATIONAL SCIENCE FOUNDATION
Earth Day: Disease spread among species is predictable
Study in California grassland expands understanding of biodiversity and management of emerging diseases

On Earth Day, a study of disease dynamics in a California grassland has revealed fundamental principles underlying the spread of pathogens, or disease-causing microbes, among species.

The results, announced today in the journal Nature, have implications for the maintenance of biodiversity and for addressing practical problems related to plant disease.

Researchers at the University of California, Santa Cruz, studied the phenomenon of "pathogen spillover" in grassland species on the UC Santa Cruz campus.

They found that the amount of disease present on each species could be predicted by the abundance of its close relatives in the grassland. When there were many individuals of the same or similar species living close together, pathogens spread more quickly.

Perhaps unexpectedly, that in turn promotes biodiversity by creating openings for less common species that are not attacked by these same pathogens.

Link between community structure and individual disease vulnerability

The findings reveal a tight link between the structure of a plant community and the vulnerability of individual species to disease.

"These scientists demonstrate that the relatedness of species in communities is an important predictor of disease prevalence," said Alan Tessier, acting director of the National Science Foundation's (NSF) Division of Environmental Biology, which funded the research.

The researchers were able to predict which plant species introduced into the grassland would be most strongly affected by naturally-occurring diseases.

Ingrid Parker, an ecologist and evolutionary biologist at UC Santa Cruz and first author of the paper, said the study adds an important new dimension to a longstanding concept in ecology known as the "rare species advantage."

Diseases take greater toll on common species

"The rare species advantage is thought to be a major driver of biodiversity in natural ecosystems," Parker said. "Most pathogens are not host specialists--they can easily move from one species to another. Whether pathogens 'spill over' depends on how closely related other species nearby are.

"Our study shows that it's the structure of the whole community around a species that affects its vulnerability to disease."

Large-scale experiment with 44 plant species

In a large-scale experiment, the researchers introduced 44 plant species from outside California. (The plants were removed before they reproduced.)

The biologists found that species with few close relatives in the grassland escaped disease, while those closely related to many resident species always showed high levels of disease.

The researchers were able to make surprisingly accurate predictions of disease in introduced species based on their phylogenetic, or evolutionary, distance from local species.

"It was kind of shocking how well we were able to predict disease at a local scale," Parker said.

Modeling "PhyloSusceptibility"

To incorporate the phylogenetic distance between species into their predictions of disease dynamics, the researchers used a "PhyloSusceptibility model" developed by scientist Gregory Gilbert at UC Santa Cruz and two other paper co-authors, Roger Magarey and Karl Suiter of North Carolina State University, who work with the U.S. Department of Agriculture's (USDA) Animal and Plant Health Inspection Service.

The model is based on USDA's global database of fungal pathogens and host plants, and can be used to predict the probability of two species sharing a pathogen.

"If a plant pathogen from Brazil suddenly shows up in southern California, you want to know what plants in California are most likely to be attacked," Gilbert said.

By showing that the PhyloSusceptibility model makes accurate predictions, the results suggest a range of potential applications.

The PhyloSusceptibility model could help avoid disease problems affecting proposed horticultural imports or reforestation projects.

It could also be used in agriculture to design intercropping or rotation systems to decrease crop disease.

Vulnerability of local species to "pathogen spillover"

Imported plants can bring new pathogens and pests into an area. The PhyloSusceptibility model could be used to assess the vulnerability of local species to pathogen spillover from such plant introductions, the scientists say.

While the PhyloSusceptibility model used in this study was based on data for fungal pathogens, Gilbert said the team has also created versions based on data for eight other groups of pests and pathogens, including insects, nematodes, bacteria and viruses.

In addition to Parker, Gilbert, Magarey and Suiter, the co-authors of the study include UC Santa Cruz researchers Megan Saunders, Megan Bontrager, Andrew Weitz and Rebecca Hendricks.

USDA also funded the work.
-NSF-
Media Contacts
Cheryl Dybas, NSF

NSF FUNDS STUDYING ECO-EPIDEMOLOGY OF LEPTOSPIROSIS

FROM:  NATIONAL SCIENCE FOUNDATION
Field fever, harvest fever, rat catcher's yellows: Leptospirosis by any name is a serious disease

Infection is more prevalent in lower-income tropical areas
Rat catcher's yellows, field fever, harvest fever, black jaundice.

All are names for the same disease, leptospirosis, an infection caused by corkscrew-shaped bacteria called Leptospira.

Symptoms range from mild--headaches, muscle aches, fever--to more severe conditions, such as meningitis and bleeding from the lungs.

Looking for leptospirosis

"Leptospira bacteria are maintained through a complex transmission cycle," write scientist Claudia Munoz-Zanzi of the University of Minnesota and colleagues in a 2014 paper in the American Journal of Tropical Medicine.

"Humans and other mammals, domestic and wild, become infected after contact with urine from an infected host, or Leptospira-contaminated water or damp soil."

Some 7 to 10 million people contract leptospirosis each year. The disease is most prevalent in tropical areas, but may be found almost anywhere that's warm and wet.

In the developed world, leptospirosis occurs in people involved in outdoor activities, such as canoeing and kayaking in warm places. In developing countries, the disease largely happens to farmers and poorer people who live in cities.

Infection with Leptospira is linked with agricultural practices, fouling of household or recreational water, poor housing and waste disposal, and changes in the density or proximity of infected animals such as rodents, domestic animals like dogs and wildlife.

Rodents most common carriers

Rodents are the most common reservoirs of Leptospira, says Munoz-Zanzi.

With a grant from the National Science Foundation (NSF)-National Institutes of Health-U.S. Department of Agriculture Ecology and Evolution of Infectious Diseases (EEID) program, Munoz-Zanzi is studying the eco-epidemiology of leptospirosis.

Awards through the EEID program fund scientists to study how large-scale environmental events--such as habitat destruction and climate variability--alter the risks of viral, parasitic and bacterial diseases.

Munoz-Zanzi's goal is to improve knowledge of the social, epidemiological and ecological factors influencing leptospirosis in South America. She and colleagues are working to identify intervention strategies to reduce the disease's effect on the health of humans and other animals.

South-central Chile: a perfect home for Leptospira?

The study is taking place in the Los Rios region of south-central Chile. The area's climate is moderate, with an economy that's based on farming, agriculture, forestry and tourism.

Most of the region's human population is concentrated in a few urban centers, with the rest scattered in small towns or villages and farm areas.

Munoz-Zanzi's research involves contrasting leptospirosis in three community types: urban slums, rural villages, and farms.

Initial findings from the research showed that 20 percent of leptospirosis starts with rodents, including rats and mice, inside households and in other environments in populated areas.

Leptospira-carrying rodents turned out to be more abundant in rural villages than slums and farms.

"Social factors can be important causes of diseases," says Sam Scheiner, NSF EEID program director. "This study shows that the type of community can determine the presence of rats and mice that are disease-carriers. The results have implications for the control of many infectious diseases."

Danger in a puddle

"Because Leptospira live in water and soil," Munoz-Zanzi says, "the environment plays a key role in transmission in household pets, farm animals and people."

When the scientists collected water from puddles, containers, animal troughs, rivers, canals and drinking water, all showed contamination with Leptospira.

In households where puddles were found along with signs of rodent infestations, leptospirosis was common.

"However," says Munoz-Zanzi, "that was true only in lower income houses."

Some 19 percent of samples from these households--most from locations with warmer temperatures, and many with dogs as pets--tested positive.

Community setting important

The scientists are now examining leptospirosis in dogs and livestock, as well as in humans. They're integrating molecular, epidemiological and other data to gain insights into patterns of infection in various community types.

"The more we understand about this disease," says Munoz-Zanzi, "the more we realize the importance of the local community setting."

Ongoing efforts, she says, include the use of mathematical models to develop recommendations for disease control that's locally relevant. The scientists hope to provide people living in the most affected areas with tools to decrease the effects of leptospirosis.

In the meantime, how can people avoid contracting the disease?

"Wear protective equipment to prevent contact with potentially infected animals and environments," says Munoz-Zanzi, "wash after any such contact, and reduce rodents in places where people live and work."

Crowded tropical conditions where rats and mice freely run from house to house may herald another unwanted guest: Leptospira.

-- Cheryl Dybas, NSF

NASA VIDEO: SCIENCECASTS: SUBTRACTING GRAVITY FROM ALZHEIMER'S

GENE EDITITING AND REGULATION TO IMPROVE IMMUNE SYSTEM

FROM:  NATIONAL SCIENCE FOUNDATION
Rewriting genetic information to prevent disease

Breakthrough Prize winner harnesses CRISPR to improve immune system
For the last few years, scientists have been studying an ancient but only recently understood mechanism of bacterial immunity that has the potential to provide immeasurable benefits to plant and animal health.

The phenomenon known as CRISPR (for Clustered Regularly Interspaced Short Palindromic Repeats) is a natural immune system found in many bacteria with the ability to identify and destroy the genomes of invading viruses and plasmids.

Researchers are trying to harness this system for gene editing and regulation, a process that could transform "the genome of plants or animals in ways that will improve their health, or introduce genetic changes that will resist disease of climate change," says Jennifer Doudna, a Howard Hughes Medical Institute investigator and professor of biochemistry, biophysics and structural biology at the University of California, Berkeley. "The explosion of research using this technique has been amazing."

Doudna, collaborating with Emmanuelle Charpentier of Sweden's Helmholtz Center for Infection Research and Umeå University, identified how the system works and engineered it in new ways that broadened its scope. The two researchers, who described their work in a 2012 paper in the journal Science, developed a technique that enables the rewriting of genetic information and the correction of mutations that otherwise can cause disease, and also can knock out the cell's ability to make harmful proteins, she says.

"Many labs have shown in principle that this can be used to correct such mutations as those that occur in cystic fibrosis, or sickle cell disease," she says. "They are showing it in cell lines and lab animals. We're still some period of time away from using this in humans, but the pace in the field has been truly remarkable, and really exciting to see."

Many bacteria have this CRISPR-based immune system capable of identifying and destroying hostile invaders. Doudna and Charpentier showed that, in doing so, CRISPR produces the protein Cas9, a DNA-cutting enzyme guided by RNA, which relies on two short RNA guide sequences to find foreign DNA, then cleaves, or cuts, the target sequences, thereby muting the genes of the invaders.

Cas9 has evolved to provide protection against viruses that could infect the bacterium, and uses pieces of RNA derived from CRISPRS to direct its activity. The system is specific and efficient enough to stave off viral infections in bacteria.

Doudna and her colleagues programmed the process so that it can be directed by a single short RNA molecule; researchers who use it to edit genomes can customize the RNA so that it sends Cas9 to cleave, like "scissors," at their chosen location in the genome.

"When we figured out how it worked, we realized we could alter the design of RNA and program Cas9 to recognize any DNA sequence," she says. "One can therefore target Cas9 to any region of a genome simply by providing a short guide RNA that can pair with the region of interest. Once targeted, different versions of Cas9 can be used to activate or inhibit genes, as well as make target cuts within the genome. Depending on the experimental design, research can use these latter cuts to either disrupt genes or replace them with newly engineered versions."

Recently Douda and Charpentier and four other scientists received the Breakthrough Prize in life sciences, which honors transformative advances toward understanding living systems and extending human life. The prizes recognize pioneering work in physics, genetics, cosmology, neurology and mathematics, and carry a $3 million award for each researcher. The Breakthrough committee specifically cited Doudna and Charpentier for their advances in understanding the CRISPR mechanism.

Doudna has been the recipient of several National Science Foundation (NSF) grants to support her research in recent years totaling more than $1.5 million. In 2000, she received NSF's prestigious $500,000 Alan T. Waterman Award, which recognizes an outstanding young researcher in any field of science or engineering supported by NSF.

She also was a founder of the Innovative Genomics Initiative, established in 2014 at the Li Ka Shing Center for Genomic Engineering at UC Berkeley. Its goal is to promote and support genome editing research and technology in both academic and commercial research communities.

"We have a team of scientists working with various collaborative partners," she says. "We want to ensure that the technology gets into as many hands as possible, and explore ways to make it even better. We are trying to bring about fundamental change in biological and biomedical research by enabling scientists to read and write in genomes with equal ease. It's a bold new effort that embraces a new era in genomic engineering."

-- Marlene Cimons, National Science Foundation
Investigators
Jennifer Doudna
Related Institutions/Organizations
University of California-Berkeley

NSF VIDEO: SCIENCE NATION - EVEN HEALTHY CORALS HAVE VIRUSES

NSF VIDEO: ALZHEIMER'S PATIENTS: A SURPRISE FINDING IN EXECUTIVE FUNCTION

MEASLES STILL A THREAT 50 YEARS AFTER MEASLES VACCINE APPROVED

FROM:  U.S. CENTERS FOR DISEASE CONTROL AND PREVENTION 
Press Release Measles Still Threatens Health Security
On 50th Anniversary of Measles Vaccine, Spike in Imported Measles Cases

Fifty years after the approval of an extremely effective vaccine against measles, one of the world’s most contagious diseases, the virus still poses a threat to domestic and global health security.

On an average day, 430 children – 18 every hour – die of measles worldwide. In 2011, there were an estimated 158,000 measles deaths.

In an article published on December 5 by JAMA Pediatrics, CDC’s Mark J. Papania, M.D., M.P.H., and colleagues report that United States measles elimination, announced in 2000, has been sustained through 2011. Elimination is defined as absence of continuous disease transmission for greater than 12 months. Dr. Papania and colleagues warn, however, that international importation continues, and that American doctors should suspect measles in children with high fever and rash, “especially when associated with international travel or international visitors,” and should report suspected cases to the local health department. Before the U.S. vaccination program started in 1963, measles was a year-round threat in this country. Nearly every child became infected; each year 450 to 500 people died each year, 48,000 were hospitalized, 7,000 had seizures, and about 1,000 suffered permanent brain damage or deafness.

People infected abroad continue to spark outbreaks among pockets of unvaccinated people, including infants and young children. It is still a serious illness: 1 in 5 children with measles is hospitalized. Usually there are about 60 cases per year, but 2013 saw a spike in American communities – some 175 cases and counting – virtually all linked to people who brought the infection home after foreign travel.

CDC REPORTS ON FIGHT AGAINST POLIO IN PAKISTAN AND AFGHANISTAN

FROM:  CENTERS FOR DISEASE CONTROL AND PREVENTION 

Progress and Challenges Fighting Polio in Pakistan and Afghanistan
Not reaching every child jeopardizes progress and risks re-introduction in other parts of the world

Both Pakistan and Afghanistan saw an overall decrease in wild poliovirus (WPV) cases from January – September 2013 compared with the same time period in 2012 according to data published in the Morbidity and Mortality Weekly Report (MMWR) released today by the Centers for Disease Control and Prevention (CDC).  Since 2012, transmission of indigenous WPV has been limited to three countries: Afghanistan, Pakistan, and Nigeria.  Results for Nigeria will be released in December.

Both countries still face significant challenges in reaching unvaccinated children.  Afghanistan is fighting a polio outbreak in the Eastern Region while Pakistan continues to see polio increases in the conflict-affected Federally Administered Tribal Areas (FATA), where there is a ban on polio vaccination, and in security-compromised Khyber Pakhtunkhwa Province. The potential risk of transmission to other countries highlights the need for strong ongoing global efforts to eradicate this disease.

“Although there have been setbacks, we are making progress towards global polio eradication,” said CDC Director Dr. Tom Frieden, M.D., M.P.H. “There is encouraging progress in Afghanistan, but, as long as transmission is uninterrupted in Pakistan and Nigeria, the risk for spread to other countries continues because polio anywhere presents a threat of polio everywhere."

In Afghanistan, confirmed cases of WPV dropped from 80 in 2011 to 37 in 2012.  The downward trend continues for 2013 with only eight cases confirmed during January–September 2013, compared with 26 during the same period in 2012.  All eight polio cases in 2013 were in the Eastern Region and originated from the wild poliovirus in Pakistan.

This week Afghanistan achieved a significant milestone - 12 months without any recorded cases of wild poliovirus in the traditionally polio-endemic provinces of Kandahar and Helmand, long recognized as Afghanistan's epicentres of polio.  This unprecedented progress is an endorsement of the effectiveness of the polio eradication programs and their implementation in the Southern Region.    

akistan reported a decrease from 198 WPV cases throughout the country in 2011 to 58 in 2012 in selected areas.  Fifty-two cases were reported during January–September 2013, compared with 54 cases during the same period in 2012.   However, because of additional cases since September, 2013 Pakistan has now surpassed the 2012 numbers, thus reversing the downward trend.   Eighty-four percent of cases reported since January 2012 occurred in the FATA and Khyber Pakhtunkhwa Province.

Approximately 350,000 children in the FATA have not received polio vaccines during immunization campaigns conducted since mid-2012 because local authorities have banned vaccination. In other areas of Pakistan, polio vaccination teams have encountered increased security threat-levels, hindering immunization programs.  Further multi-pronged efforts to reach children in conflict-affected and security-compromised areas will be necessary to prevent WPV re-introduction into other areas of Pakistan and other parts of the world.  This situation requires all countries to take additional public health actions to strengthen detection and strengthen protection by enhancing polio surveillance programs and intensifying vaccination efforts.

BIODIVERSITY AND DISEASE

Credit:  CIA World Factbook.

FROM: NATIONAL SCIENCE FOUNDATION
Biodiversity Protects Against Disease, Scientists Find
The richer the assortment of amphibian species in a pond, the more protection that community of frogs, toads and salamanders has against a parasitic infection that can cause severe deformities, including the growth of extra legs.

The findings, published in a paper in this week's issue of the journal Nature, support the idea that greater biodiversity in large-scale ecosystems, such as forests or grasslands, may also provide greater protection against diseases, including those that affect humans.

A larger number of mammal species in an area may curb cases of Lyme disease, while a larger number of bird species may slow the spread of West Nile virus.

"How biodiversity affects the risk of infectious diseases, including those of humans and wildlife, has become an increasingly important question," said Pieter Johnson, an ecologist and evolutionary biologist at the University of Colorado Boulder, and the lead author of the paper.

"But as it turns out, solidly testing these links with realistic experiments has proven very challenging in most systems."

Researchers have struggled to design comprehensive studies that could illuminate the possible connection between disease transmission and the number of species living in complex ecosystems.

Part of the problem is the enormous number of organisms that may need to be sampled, and the vast areas over which those organisms may roam.

This study overcame that problem by studying smaller, easier-to-sample ecosystems, the scientists say.

"The research reaches the surprising conclusion that the entire set of species in a community affects susceptibility to disease," said Doug Levey, program director in the National Science Foundation (NSF)'s Division of Environmental Biology, which funded the research. "Biodiversity matters."

Johnson and colleagues visited hundreds of ponds in California, recording the types of amphibians living there as well as the number of snails infected by the pathogen Ribeiroia ondatrae.

Snails are an intermediate host used by the parasite during part of its life cycle.

"One of the great challenges in studying the diversity-disease link has been collecting data from enough replicate systems to differentiate the influence of diversity from background 'noise,'" Johnson said.

"By collecting data from hundreds of ponds and thousands of amphibian hosts, we were able to provide a rigorous test of this hypothesis, which has relevance to a wide range of disease systems."

The researchers buttressed field observations with laboratory tests designed to measure how prone to infection each amphibian species is, and by creating pond replicas using large plastic tubs stocked with tadpoles that were exposed to a known number of parasites.

All the experiments told the same story.

Greater biodiversity reduced the number of amphibian infections and the number of deformed frogs.

The scientists spent three years sampling 345 wetlands and recording malformations--which include missing, misshapen or extra sets of hind legs--caused by parasitic infections in 24,215 amphibians.

The results showed that ponds with half a dozen amphibian species had a 78 percent reduction in parasite transmission compared to ponds with just one amphibian species.

The reason for the decline in parasitic infections as biodiversity increases is likely related to the fact that ponds add amphibian species in a predictable pattern, with the first species to appear being the most prone to infection and the later species to appear being the least prone.

The researchers found that in a pond with just one type of amphibian, that amphibian was almost always the Pacific chorus frog, a creature that's able to rapidly reproduce and quickly colonize wetland habitats, but which is also especially vulnerable to infection and parasite-induced deformities.

On the other hand, the California tiger salamander was typically one of the last species to be added to a pond community--and also one of the most resistant to parasitic infection.

Therefore, in a pond with greater biodiversity, parasites have a higher chance of encountering an amphibian that is resistant to infection, lowering the overall success rate of transmission between infected snails and amphibians.

This same pattern--of less diverse communities being made up of species that are more susceptible to disease infection--may well play out in more complex ecosystems, Johnson said.

That's because species that disperse quickly across ecosystems appear to trade off the ability to quickly reproduce with the ability to develop disease resistance.

The recent study also reinforces the connection between deformed frogs and parasitic infection.

In the mid-1990s reports of frogs with extra, missing or misshapen legs skyrocketed, attracting widespread attention in the media and motivating scientists to try to figure out the cause.

Johnson was among the researchers who found evidence of a link between infection with Ribeiroia and frog deformities, though the apparent rise in reports of deformations, and its underlying cause, remained controversial.

While the new study has implications beyond parasitic infections in amphibians, it does not mean that an increase in biodiversity always results in a decrease in disease, Johnson said.

Other factors also affect rates of disease transmission.

For example, a large number of mosquitoes hatching in a particular year increases the risk of contracting West Nile virus, even if there has been an increase in the biodiversity of the bird population.

Birds act as "reservoir hosts" for West Nile virus, harboring the pathogen indefinitely with no ill effects, then passing on the pathogen.

"Our results indicate that higher diversity reduces the success of pathogens in moving between hosts," Johnson said.

"But if infection pressure is high, there will still be a significant risk of disease. Biodiversity will simply dampen transmission success."

Co-authors of the paper are Dan Preston and Katie Richgels of the University of Colorado Boulder, and Jason Hoverman of Purdue University.

In addition to NSF, the research was funded by the National Geographic Society and the David and Lucile Packard Foundation.

-NSF-