Madagascar’s Plague: One Health Research Aims to Slow Its Spread

Short abstract

The integrated approach tackles a perfect storm of poverty, invasive rats, deforestation, and climate change that is contributing to the increase in bubonic plague cases.

Clad in a cobalt blue jumpsuit—the field outfit of the Pasteur Institute of Madagascar (IPM)—Malagasy scientist Adélaïde Miarinjara was tweezing fleas, one by one, from a plate of soapy water, a “candle trap” she had set the night before inside a family home. Like others in the region, the two-story house arises from the rust-red earth it is made from, topped with a palm-thatch roof. Perched on a stool outside, Miarinjara is part of a team that has responded to reports of bubonic plague outbreaks in remote villages of the plague-endemic central highlands of Madagascar.¹ On this island nation, the ancient scourge has become a modern-day nightmare, exacerbated by a perfect storm of poverty, invasive black rats, deforestation, and climate change.²

Annual numbers of plague cases in Madagascar were in the double digits from the 1950s through the end of the 1980s.³ But since 1990, there have been hundreds to thousands of cases every year.³ Why the increase? Changing climate conditions and continued habitat degradation—deforestation, for example—appear to play a part. Although estimates vary, deforestation has claimed a substantial portion of the country’s historical forest cover.^4,5

To reach outbreaks in remote areas, often in villages far from the nearest hospital, Miarinjara and other researchers sometimes travel an hour off the paved road or cross a river by ferry. Once there, they will meet with hospital staff, then the village chief. Then they will get to work baiting around 100 mesh rodent traps with fish and onion, placing them in and around homes and the verdant rice fields just beyond.

In such a village, Miarinjara counts fleas caught in candle traps, carefully placing them in vials. Other team members collect the trapped rats and mice, brushing their fur to collect their fleas. The team works efficiently, with each person calling out details of their work to a notetaker.

The candle trap, right, sits on a plant fiber–floor covering inside the home, where Miarinjiara (blue jumpsuit) and her team, left) sort and count the fleas. Images: Adélaïde Miarinjara.

Families may keep chickens, pigs, and even long-horned zebu cattle inside their homes throughout the year to protect them from theft.⁶ After the annual harvest every August, families also store rice indoors, where it becomes an attractive food source for black rats (Rattus rattus), a globally invasive rodent that thrives in rural villages. Black rats are also a primary host for Oriental rat fleas (Xenopsylla cheopis),⁷ which carry Yersinia pestis—the bacteria responsible for three deadly plague pandemics and the reshaping of societies around the world.^8–10 Plague cases on the island nation have skyrocketed since the 1990s.²

Madagascar is not alone. Human plague cases have increased globally, particularly in Africa, South America, and Asia; in 2006, the World Health Organization (WHO) declared plague a reemerging disease.¹¹ Given the lack of information on plague dynamics in natural reservoirs and the impact of climate change on increased outbreak risk, “plague should be taken much more seriously by the international community,”¹² wrote a global group of experts in 2008, following several international meetings on the topic.

Research has picked up since then, with Madagascar front and center. Miarinjara is becoming a prominent figure in the fight to understand plague’s mysteries and to keep this reemerging disease from becoming the “destroyer of worlds”¹³ it once was.

The Ecology of Plague

Of the more than 2,000 species of flea, 80 have been implicated in plague transmission,¹⁴ says microbiologist Joseph Hinnebusch. Until his 2023 retirement, he headed a plague team at the US National Institute of Allergy and Infectious Diseases Rocky Mountain Laboratories in Montana. “The ecology is very complex.”

In 1914, scientists discovered that Y. pestis forms a biofilm inside rat fleas after a couple of days.¹⁵ This biofilm congeals inside the fleas’ gut, blocking the flow of the blood they feed upon. Desperate for food, an infected flea increases its feeding activity, regurgitating bacteria-ridden blood as it goes. The starving flea dies a few days later. This physiological process makes rat fleas particularly efficient vectors.¹⁶ Scientists previously thought that only those flea species that developed this gut blockage were involved in plague transmission. In recent decades, however, researchers discovered that certain fleas transmit plague bacteria within a few hours of infection. This “early-phase transmission” is independent of the biofilm and can explain the rapid spread of epidemics and epizootics (the animal version of a human epidemic).^17–19

In the enzootic cycle, plague bacteria are transmitted between fleas and rodents. Fleas may infect other mammals, whose own fleas become infected. Humans may be infected by fleas from either cycle. Transmission between people happens in a pneumonic plague outbreak. Image: Alderson et al. (2020),² under CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/deed.en).

Plague survives in wildlife reservoirs: prairie dogs in the Western United States, desert gerbils in Kazakhstan, marmots in China, and the like.¹² “Humans,” says Hinnebusch, “are quite incidental.” Y. pestis is maintained in enzootic cycles for long periods of time, meaning the bacteria circulate at low levels throughout a wildlife population without causing mass deaths.

These are punctuated by outbreaks called epizootics. In an epizootic, higher numbers of wild or peri-domestic rodents (those adapted to live near human habitation) become infected with plague, often leading to them to die en masse.^1,20 Little is known about what leads to sudden bursts in Y. pestis activity, but some research suggests the bacterium can remain dormant in soil for months, possibly years.^21–23

Once a host population crashes during an epizootic, fleas—the plague vector—seek other blood meals. Black rats, common in Malagasy rural settlements, are quite susceptible to plague,²⁴ and when the rats die, their fleas resort to feeding on humans.

The first symptoms of bubonic plague in people include fever, chills, and weakness. Next, telltale buboes (inflamed lymph nodes) appear, and bleeding under the skin may occur.²⁵ Without treatment, 40%–70% of people who get bubonic plague die.⁷ If plague reaches the lungs, it becomes pneumonic plague, which spreads rapidly from person to person through respiratory droplets and is fatal without treatment; however, it is the less common form.⁷

Although plague exists in some modernized nations, including the United States and China, their health care systems can easily treat the disease with antibiotics before it kills or spreads—although antibiotic resistance is growing.^2,26 People in nations with poor infrastructure and inconsistent medical care—such as Madagascar and the Democratic Republic of the Congo, Africa’s two most affected nations²⁷—are not so fortunate.²⁸ Madagascar usually reports 200–400 cases a year.²⁹

“Nobody wants to declare themselves or their relatives to have plague because it’s linked to stigma around being dirty,”² says Miarinjara. “They may prefer to go to the [traditional healer] of the village, who may be closer than the medical doctors.” People developing symptoms often do not want to walk far, she notes. Delays in receiving prompt medical care, including antibiotics, result in unnecessary deaths from the disease—not to mention its spread to more people.

Curiosity Begets Discovery

Miarinjara started training with IPM in 2012 as part of her undergraduate work at Madagascar’s University of Antananarivo; she continued collaborating throughout her doctoral work, in which she studied insecticide resistance in rat fleas. “I went on investigations, and during those times, research questions were starting to bud [in my mind, but] when I’d ask the professionals, they’d say, ‘We don’t really know,’” she says. Miarinjara has continued to tackle the scientific questions she formed at that time.

Miarinjara noticed plague investigators seemed most concerned with rat fleas and the native flea, Synopsyllus fonquerniei, both of which are excellent plague vectors. But most of the fleas caught in the indoor candle traps—98%, it turns out—were human fleas, Pulex irritans.³⁰ “More importantly,” she says, “this species had been found to be infected by the plague microbe.”³¹

After counting fleas from candle traps and rat fur alike, the Malagasy team places them in ethanol to be identified, sexed, and tested for Y. pestis back in the lab. For many years, researchers disregarded the role of human fleas. “People would say, ‘If [human fleas are] a vector, shouldn’t we have more bubonic plague cases in Madagascar?’” Miarinjara explains. She wondered whether human fleas, even if less effective at spreading plague, could have a role in outbreaks due to the high numbers found in homes.

The tenrec, left, a native hedgehog, may be infected by fleas from the invasive black rat, bottom right. Transmission via another invasive species, the urban Norway rat, top right, becomes important during times of flood, when they are driven from their burrows. Images, clockwise from left: © iStock.com/dennisvdw, © iStock.com/BiZhaMox, © iStock.com/Carlos Aranguiz.

Her curious mind carried her across oceans and continents to Hinnebusch’s Montana lab in 2018, where she was able to systematically address the role of human fleas in plague transmission. “Adélaïde was looking for a postdoc [opportunity] and I thought, ‘Where is plague most important? It’s in Madagascar,’ so I thought it would be [beneficial] to train a Malagasy scientist,” says Hinnebusch. He described his three-decade career as being spent surrounded by liter-jar colonies of rat fleas, studying genes and factors that allow Y. pestis to “evade the host immune response and become so virulent so rapidly—such a fulminant pathogen.”

Can Human Fleas Transmit Plague?

For 2 years, Miarinjara worked with him to find definitive answers on the vector efficiency of human fleas, “systematically and convincingly, with well-controlled experiments,” says Hinnebusch. Until her work, “it was hard to draw any firm conclusions about the potential role of the human flea in Madagascar,” he says. “There was a lot of conflicting information.”

“[Adélaïde] came highly recommended, but when she got here, she floored me. She is really an exceptional person,” says Hinnebusch. Not only did she have to master English—her third language after French and her native Malagasy—but she also had to acclimate to a new country and a new lab dynamic. Miarinjara took up watercolor painting to ease her isolation, creating scenes from her home country and nature, along with images of medieval plague doctors and rats. She regularly donates her paintings to Ikala STEM (https://www.ikalastem.org/), a nonprofit with a mission to promote science and education in Madagascar and to raise the profile of Malagasy women in the fields of science, technology, engineering, and mathematics.

Details from Miarinjara’s watercolors of a moody village street, left, and a sunny landscape, right. Images: Adélaïde Miarinjara.

For his part, Hinnebusch had mostly studied rat fleas. “It was only when Adélaïde came that I started to think about other fleas, the natural ecology, and the human plague situation,” he says. Together, they verified that although human fleas spread plague using biofilm-independent early-phase transmission, they are poor vectors, particularly if they ingest plague-infected human blood. The fleas showed slight improvement in transmission efficiency when ingesting rat blood, due to the occasional formation of a biofilm blockage.³² However, more than 30% of the P. irritans tested maintained high bacterial loads for as long as 20 days after infection, suggesting the species may indeed play a role in plague transmission; even poor vectors can be important if there are enough of them.³²

Researchers have since found plague-infected human fleas in Malagasy villages during outbreaks.³¹ Now, more scientists are acknowledging the role of this species in spreading plague from one person to another, without the need for a rat intermediary.³³

However, Miarinjara’s study involved P. irritans from burrowing owls and red foxes. “Even if the fleas are of the same species, they are from a totally different ecosystem here in the United States. Owls have not evolved with the plague,” adds Miarinjara. “Now, I’m trying to figure out if the same results can be expected from [P. irritans] collected in [Malagasy] human settlements.”

The One Health Approach

Over the past decade or so, Miarinjara, IPM investigators, and other researchers have recognized the importance of taking a holistic, transdisciplinary One Health³⁴ approach to studying plague.^35,36 Their goal is to simultaneously address the health of ecosystems, domestic animals, and people and their livelihoods.³⁷ Broad factors such as habitat degradation, deforestation, and changing climate seem to affect plague outbreaks, as do—on a smaller scale—a home’s building materials, living conditions, and domestic animal care.³⁸

Few trees remain in this highlands landscape with a village, center right, fields beyond, and rice paddies in the foreground. Image: Adélaïde Miarinjara.

“The One Health approach allows us to improve health outcomes by creating interdisciplinary teams that integrate diverse skill sets,” says Thomas Gillespie, a professor of environmental sciences and environmental health at Emory University. Miarinjara began a second postdoctoral fellowship at Emory in 2020, after receiving the prestigious international Branco Weiss Fellowship.

“There are sometimes [clashing] egos between the medical world, the veterinary world, and the ecological world, and we don’t have time for any of that,” says Gillespie. “The key [to One Health] is that individual collaborators are open to different perspectives.”

IPM scientist Minoarisoa Rajerison, who heads its Plague Unit and works with Gillespie and Miarinjara, emphasizes the value of such collaboration. “Understanding the persistence of plague in Madagascar … requires a multidisciplinary approach: plague ecology, vector and rodent biology, diagnostics, vaccine development, genomics, and systems biology of infection,” she says. Multidisciplinary expertise and global partnerships, Miarinjara adds, allow IPM and its partners to make significant progress toward mitigating plague’s impact on public health while simultaneously promoting sustainable development in plague-affected regions.

Miarinjara, for her part, is currently focusing on communities that have historically worked with the IPM and Centre ValBio (https://www.stonybrook.edu/commcms/centre-valbio/), an international research station at the edge of Ranomafana National Park. “One of my research questions is understanding what makes [some] districts … more prone to plague than others,” says Miarinjara. “Even if they are all within the same plague risk area, the risk is not the same.” By piggybacking on previous studies, she has access to background data on regional plague histories. In addition, she notes that villagers who have previously worked with Centre ValBio more readily participate in her studies.

The collaborators’ first project involved mixed methods research—interviewing families and counting fleas—to discover reasons for the observed variation in human flea numbers from home to home. “The variation in terms of flea number per household is huge,” she says. “For houses located next to one another, just a few feet away, one may have 500 fleas, and the other one might have just 3 or 4,” says Miarinjara.

In a newly published study,³⁹ the team found high P. irritans loads in traditional mud or brick homes that had dirt floors covered with a plant fiber mat—approximately one-third of houses. Simulation models, developed with Miarinjara’s earlier transmission efficiency data, showed that the same group of households had an increased risk of plague transmission from human fleas, indicating plague might be linked to social status and poverty. The humid microclimate underneath the fiber mats provides excellent breeding sites for fleas, says Miarinjara. When people clean their homes, they typically do not remove their mat every time.

Miarinjara is now thinking about her next step. “There are already programs targeting home improvement, so it would be interesting to do flea sampling in the participating homes before and after [an intervention], to see if we can solve the problem by changing just one parameter,” she says.

Zebu, left, and other livestock may be kept indoors for protection—along with rice, after the fall harvest. Fleas persist under the plant fiber mats, right, used as floor coverings.

Climate, Deforestation, and Worsening Plague

Each year, plague cases have inevitably begun appearing around September or October, not long after the annual rice harvest in August.¹ Now, cases seem to be coming earlier in the year, which Gillespie connects with climate-related shifts in the dry and rainy seasons, warming temperatures, and stronger storms.^40,41 “We’re seeing far more catastrophic cyclones [in Madagascar],” says Gillespie. “We’re getting more per year, and they’re huge.”

The island’s worst plague epidemic to date occurred in 2017, when the less-common pneumonic plague spread rapidly in urban areas,^42,43 leading to thousands of cases. Interestingly, this spike in cases occurred just a few months after Cyclone Enawo—the worst in a decade—had caused extensive flooding.⁴⁴ According to anecdotal reports, flooded rat burrows pushed urban Norway rats (Rattus norvegicus) into closer contact with people.⁴⁵ These invasive rats usually play less of a role in plague transmission. They live mainly in urban sewer systems and are more resistant to plague, so their fleas do not have to seek other hosts.¹ Flooding of the sewer systems, however, can push them into closer proximity to human dwellings.

Climate change is also exacerbating fires, which spread across the island every year. Fires are most often intentionally set, by farmers clearing land for crops and pastures,^46,47 and also by vandals. “Every October, Madagascar is just smoke everywhere,” Gillespie says. Pointing to changing weather patterns, he says, “You have a difference in rainfall and in other conditions that make [any] fire burn stronger or spread further.”⁴⁸ Fires set to clear land can take off across the grasslands that have replaced native forests.⁴⁷ When native rodents flee from burning areas, they interact with peri-domestic rodents, increasing the risk of disease transmission.

Gillespie says that disease outbreaks tend to be more severe every 5 to 7 years, related to the severity of burning and, possibly, dynamics of the El Niño-Southern Oscillation.⁴⁹ His team has begun investigating how fires and climate change affect rodent populations and, ultimately, plague risk.

“Plague is very much related to the environment,” says Pat Wright, a professor at Stony Brook University and one of the world’s foremost lemur experts. “When you get lots of rain, you can grow lots of rice. When you have lots of rice, rats multiply; and when you have lots of rats, then you also have lots of plague.” Wright is a pioneer in connecting conservation to human livelihoods through the Centre ValBio, which she founded in 2003. “It seems like such an old-fashioned disease, and it’s not found in too many countries these days,” she says, “but it certainly is found in Madagascar, in the rural regions.”

Villagers harvest rice, which in many cases is stored indoors, attracting invasive black rats. Image: © iStock.com/pierivb.

“We’ve been doing work to understand the natural diversity of rodents and other mammals in the Ranomafana forest and elsewhere, and we’re finding black rats far deeper in the forest than we ever expected,” says Gillespie, who works with Wright. “They’re making their way in and displacing native species, taking on behaviors like burrowing and living without a dependence on people.” What that means is these peri-domestic rodents may bring plague-ridden fleas to Madagascar’s unique wildlife species,⁵⁰ such as tenrecs (native hedgehogs), which have been found infected with Y. pestis.⁵¹ No one knows if plague affects lemurs, but one study found the closer they lived to human settlements, the more likely they were to harbor genes in their gut microbiomes that were resistant to the antibiotics used to treat plague.⁵²

Modeling Climate Change Impacts

When 20th century plague records from the former Soviet Union’s extensive surveillance and eradication efforts became available to Western scientists, researchers seized the opportunity to analyze the data.^53,54 “Like many people I have met afterward, I was completely unaware that plague still existed. To me it was a medieval disease,” says Boris Schmid, a senior researcher at the Netherlands’ Wageningen University and Research. He began studying climate and plague in 2010. “It’s been a fascinating topic to explore.”

Schmid and colleagues found that historical waves of plague in Europe (from the 14th to 19th centuries) were associated with climate-driven spikes in populations of plague-infected rodents arriving from central Asia.⁵⁵ Historically, plague spread during droughts that followed years with warm springs and wet summers.⁵⁶

One of Schmid’s former collaborators, Nils Christian Stenseth, a professor of ecology and evolution at the University of Oslo, also found that plague prevalence in gerbils in Kazakhstan’s PreBalkhash desert (where the disease has persisted for thousands of years) was positively affected by warmer springs and wetter summers—although it can also spread rapidly after drought.⁵⁷ In a study published in 2006, Stenseth and colleagues estimated that in Asia, a 1°C increase in average monthly temperatures in the spring would increase plague prevalence in rodents by more than 50% (from 0.8% to 1.2%).⁵⁷ “In public health terms, a single [bacteriologically] positive sample close to human habitation is deemed sufficient to warrant control intervention,” they wrote. “Plague is a serious concern at the 0.8% average level and will certainly be even more so at a 1.2% level.”

In the United States, Schmid has modeled how climate change has affected plague in Western states.⁵⁸ Using data from 1950 to 2017, he found increased risks for rodents and humans at altitudes greater than 2,000 m. Although risk was low to begin with, observed trends of increasing temperature and precipitation were positively associated with an increased chance for the presence of plague; area suitable for plague across the region increased by 5%, particularly at higher altitudes. Measurements of the proportion of coyotes that had eaten a plague-infected rodent at some point in their lifetime rose from about 13% to 16%, Schmid says. “That doesn’t reflect a huge change in how many ground squirrels and other rodents in the USA have plague. It is still likely to be somewhere below 1%.”

The impact of climate change on plague risk lies not so much in the weather itself but in the population upheavals it causes, Schmid suggests. “I think this is a generalization you can make across the world.” When social structure breaks down, the disease often pops up, as with cholera in refugee camps and disaster areas.⁵⁹ “Regions where climate change causes more poverty and that already have plague-infected rodents will see more [human cases of] plague,” Schmid says. “Those regions that get the chance to continue to develop the wealth of their people should have less and less risk.” Development of roads, improving access to health care, educating locals about plague symptoms and treatment, and other interventions can reduce both poverty and diseases such as plague.⁶⁰

Fieldworkers carry rat traps (red) to a remote village, left. Rice grows in the foreground of this detail from one of Miarinjara’s paintings, right. Images: Adélaïde Miarinjara.

Building on Local Roots

Involving local communities is a crucial part of such strategies,⁶⁰ and local researchers such as Miarinjara can play a vital role. “Villagers are always surprised that researchers are interested in their daily problems like flea infestation,” she says. “When we explain the reason, they feel grateful that people are trying to find solutions.”

Miarinjara adds that fieldwork involves not only data collection, but also gaining villagers’ trust. “Sometimes, it is sitting patiently with mothers or grandmothers and listening to their woes, or meeting farmers in their field complaining about how bad the crop was last year,” she says. “I love these moments because they are the connection that I need to keep me going and help me to gather future directions for research.”

Mothers and fathers often say they wished their children could study and pursue the same path she did. “Sometimes I feel like I’m representing a country,” says Miarinjara. “If I do well, I might inspire more girls and women from my country to pursue education.” And the more who become educated, the more likely they may someday, once and for all, find solutions that effectively control plague while improving the wealth and well-being of the nation and its people.

Biography

Wendee Nicole is an award-winning science writer based in San Diego. She has written for Scientific American, Discover, Nature, and other publications.