Climate change, pathogens, and people: The challenges of monitoring a moving target

January 18, 2019 | Bioscience | by Lesley Evans Ogden

As the global climate changes, its effects on the environment are increasingly evident. Average global temperatures are rising, precipitation patterns are shifting, and the frequency of extreme weather events is growing, with impacts on the distribution and viability of all life forms.

For human health, one emerging concern is that we do not fully understand how the geographic ranges of vector-borne diseases—those caused by parasites, bacteria, and viruses transmitted to humans via an intermediate host organism—are being influenced by climate change. According to the World Health Organization (WHO), major vector-borne diseases account for about 17 percent of all infectious diseases and lead to 700,000 deaths per year.

The biggest burden of such diseases falls on tropical and subtropical regions and disproportionately affect the world's poorest populations. But as our planet warms, those in temperate regions and developed nations are being affected too. Research is under way to reveal clues and predictive tools for determining where diseases might be located in the future.

As our understanding of disease risks and their changing distribution emerges, there is hope that our ability to prepare for and mitigate their impacts will advance alongside.

Research roots

Disease ecologist Rick Ostfeld, based at the Cary Institute of Ecosystem Studies in Millbrook, New York, has spent much of the past 25 years focused on studying tick- and mosquito-borne disease. As he explains, many disease vectors are affected by temperature and susceptible to desiccation because they are ectothermic—their body temperatures fluctuate with the environment. Ostfeld's research has been probing how climate change will affect these organisms.

mouse catch — Richard Ostfeld, a disease ecologist with the Cary Institute of Ecosystem Studies, tries to coax a white-footed mouse (a carrier for Lyme disease), out of a trap and into a plastic bag, from which it will be removed, marked with a metal ear tag, and inspected before release. Credit: Pamela Freeman.

Tracing climate change and disease research to its roots, Ostfeld explains that early ideas about which factors regulated animal populations were highly entrenched. "There were really acrimonious debates back in the 1950s and '60s," he says, in which "ecologists fought about whether biotic [intrinsic] or abiotic [extrinsic] factors were more important in regulating animal populations." The answer was that both were important, he explains, although for particular species or at particular places and times, one might outrank the other.

Those ecological arguments were "in hindsight, kind of silly," he says, but when it came to consideration of what determined the distribution and spread of disease, they set the stage for modern-day debates over the importance of climate change to disease.

Another parallel line of inquiry fueled a debate that emerged around the mid-1990s about the idea that a warmer world would be a sicker world. People carved out opposing viewpoints that could be boiled down to "yes" or "no," Ostfeld explains. "I took a little umbrage at the kind of superficiality of some of the territory that people staked out on either side," he says.

Péter Molnár, whose research at the University of Toronto Scarborough is focused largely on modeling the ecological impacts of climate change and understanding the range expansion of parasites, says that early assumptions from the late 1990s and early 2000s were incomplete. Early researchers recognized that many pathogens and their vectors are temperature sensitive. When temperatures are higher, vector development speeds up, with faster completion of life cycles. The assumption was that faster development would mean more generations of parasites per season and an extended season for transmission, which benefits the pathogen. But that, explains Molnár, is only half of the story. "Temperature does not just affect the development rate. It also affects the survival rate in the exact opposite direction," he says, meaning that lifespans are shorter when it is warmer. Pathogens and vectors die faster when it is warm, underlining that relationships between organisms and the temperature of their surroundings are complex. There are positive and negative effects of any environmental change, says Molnár. Therefore, "a warmer world is not necessarily going to be a sicker world. It's going to be more idiosyncratic than that," he says.

The field has moved beyond this polarized "warmer means sicker" debate, now engaging in more sophisticated inquiry. Along with four coauthors, Ostfeld published a review paper in Science in 2013 outlining some of the mechanisms behind climate-induced changes in infectious disease risk and frameworks for predicting host–pathogen responses to climate change, particularly to changes in temperature.

Subsequently, there has been much progress in the area, but it is slow, says Ostfeld. One area of progress has been the use of rigorous experimentation—in the field and in the lab—to look at the effect of climatic factors on vector and pathogen life history variables. Another focus has been attention not just on annual or seasonal means but on variability at shorter timescales.

Lyme disease spread far beyond Connecticut

One disease for which there is great interest and concern regarding climate change links is Lyme disease. Old Lyme, Connecticut, was the site of the first recognized outbreak in 1975, when public health officials attributed a cluster of children and adults with arthritis-like symptoms to an unknown virus carried by an unspecified biting insect. It is now known to be caused by the bacteria Borrelia burgdorferi, transmitted to humans by the bite of an infected poppy-seed-size blacklegged tick of the genus Ixodes. Subsequently reported from forested areas of Asia; Northwestern, Central, and Eastern Europe; Canada; and the United States, it is now, according to the WHO, the most common tick-borne disease in the Northern Hemisphere. Over the decades since its discovery, Lyme disease appears to have been on the move, and peak activity times for Lyme-transmitting ticks coincide with the times people are more likely to be outdoors—during May, June, and July.

The four stages of the blacklegged tick: from left to right, adult female, adult male, nymph, larva. The tick is most likely to spread disease to humans in the nymphal stage. Credit: Alex Wolf.

Robbin Lindsay, a research scientist with the Public Health Agency of Canada, began studying the Lyme disease triad (host–parasite–pathogen) in the 1980s, when the disease was just gaining a foothold and moving in north of the US border. Back then, there was only one known well-established population of blacklegged ticks in the whole of Canada. That population was located in southern Ontario on Long Point Peninsula, a 32-kilometer-long narrow sandspit jutting into Lake Erie. Not coincidentally, Long Point is a migratory bird stopover hotspot. If birds "have ticks on them, there's an opportunity for them to drop off," says Lindsay. He investigated what environmental factors were driving ticks' development, survival, and distribution. Early on, he discovered that "differences in relative humidity had the greatest impact on their populations," he says.

For Lyme disease and for almost all of the tick-borne pathogens that make people sick, in the vast majority of cases, it is not the babies or adults but the nymphal stages that infect humans. Ostfeld is combining field work with modelling to examine how well these ticks invade new territory and persist long enough to start transmitting Lyme disease to people. Obtaining ticks locally at all phases of their development, from egg to larvae to nymph to adult stages, Ostfeld's team deploys ticks housed in containers into natural habitat, to follow their survival for two weeks while dataloggers inside the containers measure climatic conditions. "It's painstaking," says Ostfeld. Modeling converts survival data into population and transmission expectations. Ostfeld's team is 2 years into this 5-year project. Their research targets a wide latitude—from North Carolina to northern New York State—capturing a broad range of abiotic conditions, with the intent to make very specific geographic predictions about the probability of ticks' becoming established and transmitting Lyme disease.

Lyme disease–spreading ticks are now well established in Canada, and Nicholas Ogden of the Public Health Agency of Canada has been using mathematical models to test how the geographic range of arthropods such as blacklegged ticks is restricted by temperature. Most of southern and central Canada have sufficient humidity and rainfall for tick survival. The limiting climatic factor is temperature, explains Ogden. The climate must be warm enough for the tick to be able to complete its life cycle fast enough. "We think this is the main effect of climate and climate change," he says. "It's not the cold winters, it's the cool, short summers," says Ogden, that restrict this tick's survival and range. A tick's microclimate matters too. Ticks need a duff layer—the debris layer of plant fragments and leaf litter that provides a spongy habitat on the forest floor. This requirement makes agricultural land, grassland, and urban areas unsuitable. "You're not going to pick up a tick in a supermarket car park," he says. But not all disease vectors moving with climate change are less likely to be encountered in urban areas.

West Nile virus in city parks

Another vector-borne disease being examined for its relationships with climate change is the mosquito-borne illness West Nile virus (WNV). Unlike Lyme, this is a disease in which the risk of infection is not necessarily elevated with rural and wilderness pursuits such as hiking and camping. Studies in the United States, Canada, and Europe have shown that WNV is often associated with urban parks. The virus is most commonly spread to people via the bite of a mosquito that became infected when it fed on an infected bird. Humans (and also horses) are dead-end hosts for the disease, meaning that they can be infected after a mosquito bites them, but infected humans do not contribute to subsequent transmission. Even when infected, "we can't get enough level of virus in our blood to transmit to a mosquito," explains Sara Paull, disease ecologist in the Department of Ecology and Evolutionary Biology at the University of California, Santa Cruz.

WNV was first documented in the United States in 1999. Since then, the number of cases annually has fluctuated wildly, making wise allocations of public dollars difficult in light of the predictive uncertainty of the disease. Paull's ongoing research is aimed at figuring out mosquito-temperature relationships, investigating how well information from laboratory studies predicts reality in wild populations, to help improve predictive models. One puzzle, she explains, is that often in field studies, temperature is not as influential as would be predicted from lab studies. "So I'm starting to wonder if maybe the temperatures that we're inputting are not actually at the right scale," says Paull. Taking a temperature measurement from a weather station many miles away may not reflect that experienced by a mosquito hunkered down in the shade underneath some reeds. So, without taking into account microclimate, some of the temperatures being entered into models may be inaccurate, possibly explaining lab–field discrepancies.

WNV is one of many diseases under surveillance in Europe too, at the European Centre for Disease Prevention and Control (ECDC) in Stockholm, Sweden. There, Jan Semenza, ECDC's acting head of scientific assessment, explains that in Europe, WNV was until recently constrained to certain areas of southern France. That changed in 2010, with big outbreaks of the disease in Southeastern Europe that were linked to elevated summer temperatures. "We showed that temperature abnormalities, like deviation from a 30-year baseline, was a predictor of those outbreaks," says Semenza. Water availability and migratory bird patterns were also predictors, with presence of wetlands and higher concentrations of migratory birds positively associated with increased WNV outbreaks. Semenza and his colleagues developed a mathematical model to predict, on the basis of temperatures in July, the likely disease burden later in the season.

But Semenza cautions that climate is not the only factor implicated in disease emergence and expansion. His team found that in Europe, the most important driver for infectious diseases is travel and tourism. And when it comes to the drivers of disease distribution, climate change interacts with other factors in complex and sometimes unexpected ways. Nevertheless, says Semenza, even though global environmental change is not the only factor contributing to the emergence of infectious disease, his team's analysis of climate change–disease links show that "we have actually underestimated how important it is."

Malaria is highly sensitive to climate change

Erin Mordecai, assistant professor of Biology at Stanford University, heads a team using laboratory data and mathematical modeling to investigate thermal responses of vector-borne diseases. One of the diseases Mordecai investigates is malaria. According to the WHO, malaria is "the vector-borne disease most sensitive to long-term climate change." In 2016 alone, malaria caused an estimated 445,000 deaths globally. Malaria, another mosquito-borne illness, is caused by parasites of the genus Plasmodium, of which there are more than 100 species, 4 known to infect humans. Often thought of as a tropical disease, malaria was historically found in temperate areas, such as the United States, until its elimination by large-scale landscape manipulation measures in the 1950s. "Historically, that meant intentionally draining swamps and spraying DDT and things that we don't really support environmentally anymore," says Mordecai. But mosquito control continues in the United States today with local-scale spraying of pesticides that are less harmful to the environment, as well as larval habitat elimination by encouraging backyard standing water remova

Malaria was previously endemic to Western Europe too, until its elimination in the 1970s, although it became reestablished in some regions in the 1980s and 1990s. Another control program began in 1999 with a goal, successfully reached, of eliminating indigenous malaria cases by 2015. In North America and Europe, most cases of malaria are now localized and acquired via international travel, but in many tropical countries, malaria remains a major health concern.

Mordecai's work underlines what researchers were not recognizing in the early days of climate change-disease research: For every organism, temperature relationships are not simple linear trends. There are temperature limits, and the temperature can get too warm. In malaria, warm temperatures can be detrimental to the transmission process. In high temperatures, mosquitoes may not survive very long or successfully complete their life cycles. Early in her studies, Mordecai and her collaborators began looking at how temperature affects all of the processes that drive transmission—including biting, reproduction, survival, and parasite development. What they found is a unimodal, or hump-shaped, effect, meaning that there is an optimal temperature for all of these traits. For malaria, "we found an optimal temperature of 25 degrees Celsius [°C]," says Mordecai.

Past research had not accounted for these hump-shaped relationships between temperature and mosquito traits. The result was that they overestimated the optimum temperature to be 32°C, and predicted that with climate change, malaria transmission would increase everywhere. Publishing their work in a 2012 paper in Ecology Letters, Mordecai says, "Our research started to show that malaria transmission was more likely to shift in distribution and seasonality rather than increase around the globe." Mapping out this newly refined relationship in a 2015 paper for Vector-Borne and Zoonotic Diseases, she and her collaborators found three important implications. First, regions with an ideal temperature for malaria transmission occupied a larger area of Africa than previously supposed. Second, under climate projections, they predicted a modest increase in overall area suitable for malaria transmission. Third, they projected that under climate change, there would be a net decrease in the most suitable area. Combining their projections with those for human population density projected until 2080, their mapping suggested that hotspots of highest-risk malaria transmission will shift eastward and southward from coastal West Africa toward the higher elevation and densely populated east African Albertine Rift region.

Now, in a new project funded by the National Science Foundation Ecology and Evolution of Infectious Diseases Program, Mordecai is working to apply the same principles she used in studying malaria to predict thermal responses in 13 other vector-borne diseases, including dengue, chikungunya, Zika, and WNV.

Knowledge gaps, responses, and future planning

Many knowledge gaps remain in understanding how climate change affects the distribution of vector-borne diseases. Lack of data is one major problem. Insufficient funds and people power limit the number of diseases that can be studied. "We maybe understand 1000 pathogens very well," says Molnár. Researchers typically focus on those that affect humans and livestock. "Of these, we only understand for a handful how temperature changes affect them," he says. There are thousands of worm parasites alone, explains Molnár. Add bacteria and viruses, and the numbers are in the millions. "The bottom line is, we only have data to make these climate change predictions for the best studied diseases. For everything else, we need to come up with proxies, or we need to collect more data. That's a huge limitation in the understanding of everything that's going on," he says. He is searching for generalities within the well-understood diseases to allow rough forecasts for others.

Getting the right kind of climate data is another gap. "Off the peg climate data is not what we need," says Ogden of Canada's Public Health Agency. Getting the right kind of climate data for short- and medium-term projections is a challenge echoed by Semenza. Among the possible critical data needed for predicting disease distribution and risk are coldest temperature in winter, hottest temperature in summer, variability in temperature, or a wide range of other nontemperature climate variables. To use climate model projections effectively, disease ecologists and epidemiologists need to work closely with climatologists. "It's always hard to get people to work outside of their silos," says Lindsay, Ogden's colleague, but the situation is improving with increased funding opportunities for cross-disciplinary collaboration, especially in Europe. Globally, the "One Health" initiative, a large international collaboration, is attempting to foster broad-scale collaboration among experts in individual, population, and ecosystem health, for the benefit of humans and animals.

In terms of disease surveillance, diagnosis and detection of Lyme and other diseases can be challenging. For Lyme disease and WNV, there are no currently licensed human vaccines. Treatment options, when they exist at all, are limited, with antibiotics being employed to treat diagnosed or suspected Lyme disease but no current treatment for West Nile other than supportive care of symptoms, placing the spotlight on prevention of infection as an important priority.

As vector-borne diseases exploit new regions as climate changes, "Vaccination programs might be helpful in some instances, if we could develop vaccines," says Kristie Ebi, public health scientist at the University of Washington's Center for Health and the Global Environment. She also points to the importance of investments in strengthening health systems. Surveillance and control programs like mosquito habitat removal already have demonstrated effects on where particular vector-borne diseases emerge. More proactive and effective interventions; surveillance programs; investment in research and development for tracking, prevention, and treatment; raising the awareness of health care professionals and the general public; and development and improvement of early-warning systems are all ways in which researchers could ultimately reduce the health risks of the change in climate, says Ebi. She participated in the June 2018 Adaptation Futures climate change conference held in Cape Town, South Africa, speaking on strengthening resilience to health risks of climate change in low and middle income countries.

Of course, says Ostfeld, "the best thing we could do to prevent the further expansion of diseases with climate change is to slow down the warming of our planet." That seems unlikely to happen any time soon. Even beyond the scientific challenges, there are political ones. But, as Semenza and his colleagues explain, in finding solutions, "Complexity is not an excuse for inaction."