NEWS FEATURE NEWS FEATURE News Feature: Many species, one health

In the race to save endangered frogs from extinction, disease ecologists are hunting for patterns of infection that could also improve human well-being.

Danielle Venton making a few ecosystem tweaks, perhaps Science Writer reintroducing a species in one location or repelling another species somewhere else. Frogs infected with the flatworm Ribeiroia the eggs release larvae that infect snails. However, by uncovering the relationships be- could be extras in a horror movie. Their bod- Once inside, the larvae reproduce asexually tween multiple pathogens and multiple hosts, ies are a tangled mess, sprouting extra limbs to produce another form of larva that creates researchers are also revealing connections andjoints,andcoveredwithstrangeskin cysts around the developing limbs of tad- between human and animal health. In the “ ” webbings and bony protrusions. No longer poles. The result is not only visually ghastly, past decade, the concept of One Health, able to walk or swim, they have become easy but a harbinger of a wider problem across first used in the 1800s to suggest crucial links prey for hungry birds and that’sexactlywhat multiple animal populations. between the health of animal and human the parasite is counting on. Work on Ribeiroia’sexploitsisonefront populations, has gained traction among Ribeiroia is a trematode, a type of flatworm in a wider campaign by a small but growing public health and disease researchers: the that lives in several hosts, jumping between group of researchers. Disease ecologists are Centers for Disease Control and Prevention frogs, birds, and snails. Once a bird eats an closely tracking and modeling disease sys- (CDC) established a One Health office in infected frog, the worms reproduce sexually tems in an ambitious bid to determine the 2009, and a year later the CDC, World within the bird’s body and their eggs hitch underlying principles of how infections Health Organization, and others devised arideonthebird’s feces, making their way spread. The work could eventually help steps to adopt a One Health approach that into ponds and marshes. When they hatch, land managers to reduce disease impacts by mingles research in animal and human

Researchers from the University of Colorado and the City of Gresham, Oregon, search for malformed amphibians in a pond near Portland, Oregon. Image courtesy of Dave Herasimtschuk © Freshwaters Illustrated.

www.pnas.org/cgi/doi/10.1073/pnas.1423578112 PNAS | February 10, 2015 | vol. 112 | no. 6 | 1647–1649 Downloaded by guest on October 2, 2021 University, California, in the late 1990s. Landowners in Santa Clara County had be- gun reporting severely malformed Pacific treefrogs (Pseudacris regilla) in their ponds, and Johnson noticed that many other species were suffering the same fate, including American bullfrogs (Rana catesbeiana), Western toads (Bufo boreas), and California newts (Taricha torosa). However, the only ponds affected were those that hosted a par- ticular group of snails, a group that is the exclusive first intermediate host of the para- site Ribeiroia ondatrae. Scientists had already raised the possibility that parasites could be the cause of the amphibian malformations based on dissec- tions of the dead and diseased animals. But Johnson and other Stanford biologists were the first to test the theory in a laboratory by exposing tadpoles to Ribeiroia larvae. Ex- tending their search across the Western states, they found nearly a dozen species of The parasitic flatworm Ribeira causes limb deformities in Northern leopard frogs such as this frogs, toads, and salamanders were vulnera- one. Image courtesy of Dave Herasimtschuk © Freshwaters Illustrated. ble to Ribeiroia-induced deformities. Infec- tion hotspots, they noticed, tended to be most – disease in hopes of stemming the spread of that inhibit the spread of disease, for exam- common along major bird flyways (1 3). pathogens among species. Proponents say ple. Alternatively, if ecological insights en- Although long-term data are hard to come that understanding disease spread among abled health officials to anticipate a likely by, Johnson believes the rate of malforma- wildlife could lead to a new approach to outbreak, they could deploy vaccines much tions caused by Ribeiroia infections has risen. fighting human infection: using ecological more quickly. A review of old field notes, historical surveys, management to prevent, predict, or control A lot more work will be needed before and dissections of old museum specimens outbreaks. Critics, though, argue that such such approaches are ready for routine use by seem to indicate that malformations used to an approach is at best an oversimplification. health agencies like the CDC. The interac- be less common. The change, he says, is prob- Whatever the case, new approaches will be tions between hosts, pathogens, and environ- ably because of a host of factors: the in- essential if future outbreaks are going to be mental factors are complex and sometimes creasing eutrophication of waterways, which delivers an oversupply of nutrients that stamped out efficiently. “We’re being con- counterintuitive. Until recently, however, boosts snail populations; growing use of fronted with emerging infectious diseases all disease ecologists have focused mainly on pesticides that reduce amphibian immunity; the time, and at an increasing rate,” says Rick simple systems involving one host and one changes in biodiversity; and shifts in bird Ostfeld, senior scientist at the Cary Institute of pathogen. These systems are relatively easy to population dynamics. “Most of the hotspot Ecosystem Studies in Millbrook, New York. model and understand, but they are not very “ realistic or useful. Researchers will have to sitesarepondsgreatlymodifiedbyhuman Theresponseofourpublichealthcommu- ” “ grapple with the fact that, as in the case of activity, says Johnson. So differentiating nity is vigorous, aggressive, and high-tech, ” ” Ribeiroia, individual hosts often harbor mul- among these factors is a bit challenging. laudable in many ways, but inadequate. Ost- It was unclear, for example, whether dis- field says that, even after an outbreak has tiple pathogens, Ostfeld says. Figuring out how all these interactions affect a pathogen’s ease-transmission rates were greater in ponds fizzled, infectious disease specialists often “ ’ with lower or higher biodiversity. On the know little about what caused the outbreak virulence is the ultimate goal, he says. That s our challenge over the next 5 to 10 years.” one hand, adding extra host species to an or how they might be able to react more ecosystem generally reduces the overall rates quickly the next time. Pond Life of disease, a phenomenon known as the di- ’ Battling outbreaks after they ve begun, says Sightings of malformed amphibians across lution effect. However, at the same time, Ostfeld, is like pouring water on a raging the Western United States have skyrocketed a broader range of host species will generally inferno. Instead, he envisions public health since the mid-1990s. In some ponds, the level support a wider variety of parasites, raising officials behaving more like fire marshals, of infection is so severe that biologists are the chances of infection (4). Each factor pulls detecting when conditions are ripe for disas- worried the disease could wipe out certain in the opposite direction, creating complex ter and acting to reduce the risk of an out- species. “We visit ponds where 70–80% of the scenarios that vary depending on the eco- break. “If some large development project is endangered species, like the California red- system and the species. going to reduce protective diversity, or cause legged frog, are so deformed they’re likely to To help solve the puzzle, Johnson and his human encroachment into dangerous habi- die,” says Pieter Johnson, a disease ecologist team ventured into hundreds of San Fran- tats, or cause vector populations to explode, at the University of Colorado, Boulder, who cisco Bay Area ponds, collecting amphibians wemightbeabletoaltertheplantoavoidthe has studied this disease system for decades. and sending them to Colorado for dissection. disease outbreak,” suggests Ostfeld. That plan Johnson began studying frog deformations “It was pretty mucky work at times,” says might involve protecting a habitat for species as an undergraduate student at Stanford doctoral student Daniel Preston. “Some of the

1648 | www.pnas.org/cgi/doi/10.1073/pnas.1423578112 Venton Downloaded by guest on October 2, 2021 trematode parasites we work with can acci- poor to the most species-rich,” he notes. Other ecology team into their viral pathogens team NEWS FEATURE dentally swim into you and cause a nasty host species tend to reduce overall tick num- to help respond to the current Ebola rash, so we always wore waders. These aren’t bers. Possums and gray squirrels, for example, outbreak. “I really do buy into the idea,” ponds you’dwantyourkidsplayingin.” gobble up ticks as they groom themselves. says Sonia Altizer, a disease ecologist at The researchers also harvested live para- “There are actually some interesting parallels the University of Georgia, Athens, who sites from snails—ofteninthemiddleofthe with Pieter’swork,” says Ostfeld. He believes studies how human changes affect the night, when the parasites were most active— that promoting rich, diverse ecosystems that spread of pathogens in wildlife. Humans and introduced them into four different types include long-lived animals should help to are putting such great demands on the of outdoor experimental enclosures. One had protect wildlife and humans against disease planet that new diseases are bound to emerge, lots of parasite species, a second had lots of (7). Keystone disease reservoirs, he says, she says. hosts, a third had plenty of both, and a fourth should be monitored and managed. Humans’ connection with other species is had few of either. Then the researchers dis- However, this suggestion—and the hunt clearly a two-way street. Although we often sected the hosts to count how many parasites for rules that apply to multiple ecosystems— think of diseases jumping from wildlife to had successfully made the jump. has been met with skepticism in some circles humans, the leap can happen in both direc- Their quantitative approach was designed of disease ecology. Retired professor of par- tions, says Altizer. Outbreaks of measles and to disentangle the relative contributions of asite ecology Sarah Randolph, formerly at the other human-spread respiratory infections, host and parasite diversity. Introducing more University of Oxford in the United Kingdom, for example, have caused disease outbreaks host species, for example, corresponded to has argued that the dilution effect is an overly and deaths among endangered chimpanzees a dramatic fall of up to 65% in Ribeiroia simple and optimistic idea. Protecting bio- in Uganda. As their habitat becomes in- infections. In the laboratory, communities diversity is intrinsically valuable, she argues, creasingly fragmented, chimpanzees overlap with three species of hosts saw about 40% leaving no need to make the case for dubious more with humans, making it more likely fewer overall parasite infections than com- utilitarian goals, such as protecting human that they will exchange illnesses. “These apes munities with just one species. A community health (4). Other researchers have said that are not in a natural situation anymore,” says relatively abundant in parasite or pathogen although conservation might improve public Julie Rushmore, one of Altizer’sformer species also saw a drop in the amount of health initiatives in some cases, the general graduate students, who has studied chim- disease transmission, although the effect was link between biodiversity and disease is weak panzees’ social networks in Kibale National not as great (5). and idiosyncratic. Disease risk is more likely Park, Uganda. “A lot of the pathogens they’re Parasite competition may be the key factor ’ a product of a host and vector sparticular exposed to are coming from humans, either behind this observation, Johnson believes. As biology, and not based on patterns of species through tourism, research, or living in parasites begin to infect a host, the hosts’ biodiversity, according to Dan Salkeld, a re- an overlapping landscape with humans,” immune systems ramp up, making it more search associate at the Stanford Woods In- she says. difficult for other types of parasite to join the stitute for the Environment in California (8). Rushmore is now developing strategies for party. That finding suggests it may be pos- Ostfeld acknowledges that it is not always administering vaccines to these endangered sible to control the disease by managing the possible to draw general rules from studies of animals when diseases strike. Her studies, biodiversity in ponds, identifying and pro- ecosystem interactions. Invasive exotic spe- based on human epidemiology, have helped moting the key species that keep Ribeiroia cies, for example, do not always displace determine which individuals are most im- in check. Similar strategies could be applied natives and damage their ecosystems. “But portant to target (9). Some apes, especially more broadly to address the global decline in the fact that there are exceptions shouldn’t amphibian populations. prevent us from applying policies that reduce high-ranking mothers, form day-care groups invasive species,” he says. to share child rearing, and these apes can Beasts in the Field become nodes of infection, just as certain Ostfeld is studying a different ecosystem to Health for All humans have been known to act as “super- investigate why some species are so good at Johnson’sandOstfeld’s work plays into the spreaders.” spreading disease. The best ones, he suggests broader “one health” idea within disease Patternslikethesemaynotbeuniversal, “live fast and die young,” and reproduce ecology. The CDC’s recently opened One but Ostfeld believes that they are worth explosively. In a recent study he suggests Health office helps veterinarians and public searching for. “Maybe it’s possible that ev- that this abundance of hosts means that health experts work with agencies like the US erything is idiosyncratic, maybe there are no a pathogen is more likely to encounter them, Department of Agriculture to control zoo- principles,” he admits, “but, on the chance and tends to be well adapted for infection notic diseases. The CDC has also brought an that there are, it’s worth pursuing them.” perfection. These hosts also may have poor immune systems, rendering them unable to resist infection (6). 1 Johnson PT, Lunde KB, Ritchie EG, Launer AE (1999) The effect of 6 Ostfeld RS, et al. Life history and demographic drivers of reservoir ’ trematode infection on amphibian limb development and survivorship. competence for three tick-borne zoonotic pathogens. PLoS ONE 9(9): Ostfeld s specialty is tick-borne Lyme dis- Science 284(5415):802–804. e107387. 2 Johnson PT, et al. (2002) Parasite (Ribeiroia ondatrae) infection ease, a potentially debilitating bacterial in- 7 Keesing F, et al. (2010) Impacts of biodiversity on the fection spread by ticks to humans, which is linked to amphibian malformations in the western United States. Ecol Monogr 72(2):151–168. emergence and transmission of infectious diseases. Nature the most commonly reported vector-borne 3 Johnson PT, Lunde KB, Zelmer DA, Werner JK (2003) Limb 468(7324):647–652. illnessintheUnitedStates.In2012,theCDC deformitipecimens and resurvey data. Conserv Biol 8 Salkeld DJ, Padgett KA, Jones JH (2013) A meta-analysis – recorded more than 30,000 probable cases of 17:1724 1737. suggesting that the relationship between biodiversity and risk of 4 Randolph SE, Dobson AD (2012) Pangloss revisited: A critique of zoonotic pathogen transmission is idiosyncratic. Ecol Lett 16(5): Lyme. The primary tick host is the white- the dilution effect and the biodiversity-buffers-disease paradigm. 679–686. “ ’ Parasitology 139(7):847–863. footed mouse, says Ostfeld. That stheguy 9 Rushmore J, et al. (2013) Social network analysis of wild ’ 5 Johnson PT, Preston DL, Hoverman JT, LaFonte BE (2013) Host and who basically never disappears, who spresent parasite diversity jointly control disease risk in complex communities. chimpanzees provides insights for predicting infectious disease risk. in all disease systems, from the most species- Proc Natl Acad Sci USA 110(42):16916–16921. J Anim Ecol 82(5):976–986.

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