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More is More: Two Bugs Are Deadlier Than One

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Associate Professor of Biology Isabella Cattadori researches the effects of coinfections on disease transmission.
More is More: Two Bugs Are Deadlier Than One

Cattadori and Emily Hake, 2nd year Biology major, Schreyers Honors College, review data.

UNIVERSITY PARK, Pa.—Rabbits with worms shed significantly more Bordetella bronchiseptica bacteria—similar to whooping cough bacteria in humans—to other rabbits than those without worms, according to Isabella Cattadori, associate professor of biology. The finding, she said, has implications for livestock and people.

“We are interested in learning, for example, whether people with pathogens like Ebola, HIV, or tuberculosis are more likely to spread the deadly infections to others if they also harbor another pathogen or parasite, such as malaria or worms,” said Cattadori. “Our research on rabbits and their common pathogens and parasites suggests that this might be the case.”
While Cattadori and her colleagues know that having a coinfection—a concurrent infection with two or more different infectious agents—in some cases increases transmission of pathogens, yet they still do not know exactly how. “Our work suggests that the immune response plays a crucial role, but this might not tell the full story,” she said.

Cattadori and her team also have observed that some of their coinfected rabbits become “super-shedders,” meaning they shed a huge amount of bacteria into the environment than other animals with the same illness. “Coinfected rabbits shed more than rabbits with just one bacterial infection,” she said. “But we have found that among the coinfected rabbits, there are individuals that disproportionally shed even more than the average coinfected cases. In other words, coinfection can turn individuals into super shedders and the probability of finding these super shedding individuals is higher among coinfected animals.”

Cattadori noted that the finding does not hold up when the animal is coinfected only with worms, but there is evidence to suggest that this is true when the animal is coinfected with other pathogens like bacteria and viruses. 

In addition to transmission, the team is investigating whether having one infection increases the likelihood of acquiring another infection, and whether having a coinfection results in the second infection causing more damage to the body.

“We have found that if a rabbit already has an infection, such as a worm or a pathogen, then the animal can be more susceptible to being infected with a second infection,” said Cattadori. “This may be the case with humans too. Think about the flu. People with the flu are more susceptible to acquiring a secondary bacterial pneumonia infection. Likewise, many of the people who are currently infected with the Ebola virus probably already have worms, malaria, or a respiratory illness. While the Ebola virus appears to be highly virulent, having other infections has probably facilitated infection and physiological complications.”

Cattadori’s research also has shown that individuals with coinfections have a more difficult time battling the infections than individuals with just one infection. “The immune system has to decide if it should fight more aggressively one infection or the other,” she said. “We are measuring the immune response to see how it balances multiple infections.”

To study the immune response, Cattadori is examining the effects of chronic infections, like worms and B. bronchiseptica, on European rabbits.

In addition, Cattadori is investigating how coinfections affect pathogen evolution by using myxoma virus and worms in rabbits. Myxoma virus is a common virus of South American rabbits, but it kills European rabbits in about 15 days. Cattadori’s hypothesis is that European rabbits infected with worms will die from myxoma virus sooner than rabbits without worms.

A rapid death is certainly not a welcome result for the patient, but it’s also not good for the virus. “Pathogens that kill too fast die out,” said Cattadori. “But the ones with some mutation that enables them to kill less quickly or not at all are the ones that are successful and stay around for much longer.”

According to Cattadori, while she and her colleagues are working on the rabbit system, the things they are learning are applicable to livestock, wildlife, and, more importantly, humans. “Having a coinfection can change everything, from your likelihood of acquiring an illness to the rate that you spread the illness to others to the treatment that is used to help you get better,” she said.