Knowledge and use of prevention measures for chikungunya virus among visitors to Virgin Islands National Park

By: Helen Beilinson

Reprinted with permission from Open Science DB. Open Science DB is a centralized database of scientific research. It is led by graduate students from Northwestern University and scientists from leading research universities/institutes contribute summaries of research papers to the database. Each summary is reviewed to ensure accuracy and accessibility. 


Pretravel health research— not something people typically think about when they’re packing their flip flops and sunscreen for a sunny vacation in the tropics. Unfortunately, mosquitos love the warm temperatures just as much as humans do. Without the knowledge of proper mosquito bite prevention strategies, vacationers are put at risk for catching viruses carried by mosquitos.
Chikungunya is caused by Chikungunya Virus that is transmitted to human by mosquitoes. Chikungunya outbreaks have been observed in countries in Africa, Asia, Europe, and the Indian and Pacific Oceans. But Chikungunya spread to Americas in 2013, and by the end of 2014, about 1 million suspected and confirmed cases of Chikungunya were reported across 43 countries in the Americas. Infected people start feeling symptoms about a week after being infected by a Chikungunya-carrying mosquito, the most common of which are a high fever and joint pain. Although most patients start feeling better within a week, many experience prolonged joint pain up to several months. There is no vaccine against Chikungunya, so the best way to prevent infection is making sure that people are educated about the virus and instilling mosquito bite prevention practices. However, there is no information regarding how many travelers are aware of Chikungunya and prevention methods.  
To answer this question, the Center for Disease Control and Prevention (CDC) investigated what percentage of travelers to the U.S. Virgin Islands are aware of mosquito-borne diseases (Chikungunya and other viruses) and mosquito bite prevention measures. Visitors to Virgin Islands National Park on St. John were asked to complete a questionnaire addressing knowledge related to mosquito-spread diseases and prevention measures .446 of 783 travelers completed the survey.
According to the survey results, more than half of respondents were unaware of Chikungunya virus. Moreover, the majority responded that they had not been wearing clothing treated with an insect repellent or long-sleeve shirts/pants, or using bed nets for the past three days.
Overall, this survey showed that most visitors arrive the U.S. Virgin Islands without adequate pre-travel research and knowledge about mosquito safety. As the number of international travelers increases each year, this survey data strongly emphasizes the urgent need for developing creative ways to encourage pre-travel health research among travelers. 

A New Science Podcast... By Yours Truly

Hi everyone!

Just wanted to pop in and promote a new science podcast that I have had the honor and privilege of creating with the Yale Journal of Biology and Medicine. It can be found on SoundCloud and iTunes. Please subscribe and listen in! Don't worry if you're not a scientist- we made this podcast specifically so we can talk about cool science that is happening without too just scientific jargon!

YJBM is a quarterly scientific journal edited by Yale medical, graduate, and professional students (me included!). Each of our issues is devoted to a focus topic that ranges from the aging brain to epigenetics to infectious diseases. With our podcast, we want audiences outside of those working in said focus topics to enjoy the research that is being done and appreciate the fields. We talk about the past, present, and future of the focus topic field. This month we're focused on the microbiome--we have cool facts (Did you know the first fecal transplant was performed in the 4th century? Or that people who live on farms are less likely to have allergies?), interviews with top clinicians and scientists, and random history facts that are great for cocktail hours. 

If you want to learn more or read about the articles in YJBM that we reference, check out the YJBM archives! They're open access so everyone can read them- you don't need special access!

The Evolution of Human Violence

By: Helen Beilinson

Why are humans violent?

This is a dense question that has been heavily debated for centuries. There are, very simply, two camps—nature and nurture. The former has been popularized by the seventeenth-century philosopher Thomas Hobbes, who argued that the natural state of man is one of violence and independent perpetuation, that humans are naturally, inherently violent. On the other hand, Jean-Jacques Rousseau retorted, nearly a century later, that individuals are not born violent or peaceful, but instead, are molded by their environments. Outside of philosophy, social scientists have tackled this distinction by focusing on the nurture side, analyzing how sex, age, race, and socio-economic status can influence an individual’s propensity towards violence. In a recent issue of Nature, Spanish scientist José Mariá Gómez and colleagues took to answering this question from a different, unique angle—evolution.

 Lethal conspecific violence, or violence occurring between members of the same species, is not unique to humans, from infanticide in primates and dolphins to horses and hamsters attacking their own. The prevalence of aggression throughout mammals, and its high inheritability, questions whether evolution has shaped human violence due to intraspecies violence being an adaptive strategy for survival. To address this question, the authors of this study used comparative methods from evolutionary biology to quantify the levels of violence in 1,024 mammalian species, including those that are currently extinct. They assessed causes of death in over 4 million instances, defining the level of lethal violence in a species as the probability of dying from intraspecific violence compared to other causes.

 Out of the analyzed species, nearly 40% had instances of conspecific lethal violence, with, on average, 0.30% of deaths within a population occurring at the hands of those in the same species. The authors calculated phylogenetic signals of related species to analyze the evolution of lethal aggression in mammals. This signal is essentially a measure of how lethally violent a particular species is in comparison to other closely related species. They found that lethal violence was entirely absent from some species, like bats and whales, and was more frequent in other groups, such as primates. Lethal violence was at similar levels in closely related species, speaking to its heritable aspect.

 Within primates, one of the most notoriously violent groups of animals, there were differences in levels of violence, indicating violence’s evolutionary flexibility. While chimpanzees were highly violent, bonobos were tamer. This observation drove the authors to ask whether other factors could influence violence within a species. The authors subsequently scored the analyzed species for territoriality and social behavior, two traits that could drive aggression. They found that social, territorial animals had high levels of lethal violence than solitary, non-territorial species.

 Studying the evolution of and phylogenetic signals for lethal violence in mammals as a whole provided a basis for studying the violence in humans. In addition to the animal species studied, 600 human populations were analyzed, ranging in time across human history, from the Paleolithic era (~2 million to 10,000 years ago) to the present.

 We emerged from the primate line, with a long evolutionary history of higher-than-average levels of conspecific lethal violence, so it is unsurprising that at the origin of our species, human lethal violence accounted for 2% of all deaths, six times higher than the reconstructed mammalian value. Additionally, we as Homo sapiens are both social and territorial, trains with stronger tendencies towards lethal violence in mammals.

 Over human history, the estimates of lethal violence vary greatly. Although Paleolithic estimates were close to 2% of deaths were due to lethal aggression, estimates rose as high as 15-30% in various times throughout history, peaking about 3,000-5,000 years ago. Today, levels of lethal violence have decreased markedly. The authors claim that socio-political organization was a significant factor in the changes in violence. They found that there was a correlated rise in violence when human moved from pre-societal organizations, including bands and tribes, to more modern organizations like chiefdoms and states. However, although high population densities in most mammalian species drive lethal aggression, in humans, population increases were consequences of successful pacification, leading to less violence.

 Although the news is packed daily with stories of human-on-human violence, today, less than 1 in 10,000 deaths (about 0.01%) are due to lethal violence. Based on the model put forth by Gómez, this translates to humans being about 200 times less violent today that can be predicted by our evolutionary past. Even a lethal violence rate of 0.01% is too high; there is a lot of social and political work that needs to be done to lower this incidence as much as possible, ideally to zero. A violent past and phylogenetically inherited lethal violence have set up modern humans to be naturally violent creatures, nevertheless, it is clear that culture, be it social or political, can strongly influence and modulate levels of aggression in a population.

The Nose Knows How to Keep Staph at Bay

By: Helen Beilinson

A year and a half ago, I had temperatures over 100°F, could barely concentrate, and couldn’t sleep for more than two hours without waking up covered in sweat. After three days of somewhat tolerating this out of body experience, I realized that this wasn’t some kind of horrible cold and went to the student health care center. I had pyelonephritis, a bacterial infection of the kidney. I spent the next week in the hospital being pumped with antibiotics. Scarily, the antibiotics I was initially given did nothing to the invasive E. coli trying to take over my body. They were resistant to the drug that was supposed to kill them. It took two days of lab tests to realize this fact, after which I was immediately switched to another antibiotic, to which my new bacterial friends were not resistant. Thankfully, I was infection free and out of the hospital soon after.

I was fortunate in that a simple switch to another antimicrobial cleared my unwelcome squatters. In many cases, infectious bacteria are resistant to multiple drugs, termed multi-drug resistant organisms (MDRO), or, more comic book-ly, ‘super-bugs’. Bacteria evolve very quickly; modifying their genomes to select what works best for their environment or even obtaining bits of DNA from other bacteria that would aid them in survival. These bits of DNA encode genes that mutate at some of the fastest rates and that are one of the most frequently transferred from one bacterium to the next. They also encode genes that induce resistance to antimicrobials. The longer certain antimicrobials are used in the clinic, the more bacteria are able to acquire resistance genes, spreading resistance from bacterium to bacterium, from species to species. The need for new antimicrobials has been terrifyingly high for the last few decades because there has not been a new class of antibiotics discovered for the treatment of bacterial infection since 1987. 
Many studies have been aimed at synthesizing new biomolecules in the lab in attempts to find a molecule never before encountered by bacteria that has antimicrobial potential. Other scientists have turned to a surprising place to find naturally occurring antimicrobials: bacteria.

Bacteria occupy what are called niches, a location that has a particular bacterium’s perfect temperature, humidity, and food. Although there are millions of niches that bacteria occupy, from lava pits to our pets’ guts, bacteria still have to compete with other bacteria for their niches. This is particularly true of locations that are not rich in nutrients—the bacteria not only have to fight for space, but also for food. To fight against invaders, bacteria use many strategies, including producing their own antimicrobials. One species of bacteria will produce molecules that harm other bacteria, while the producing species is unaffected by those molecules. These microbially-derived antimicrobial molecules have been the subjects of many scientific treasure hunts. Many niches have been explored, from the ground to the ocean (both of which have been very fruitful locations), but one recently published paper from the University of Tübingen looked for antimicrobials much closer… in their noses.

Any location on the human body that is exposed to the environment has a milieu of microbial life living in it. The nose is no exception. The nose, as well as the upper airway to which it is connected, is very nutrient poor, meaning that any bacteria that live there are in strong competition for space and food. Bacterial species from the human microbiota have been shown to produce bacteriocins, which are antimicrobial molecules. The authors of this study explored nasal commensals in attempts to identify antimicrobials capable of acting on Staphylococcus aureus, a bug that lives in the nose, respiratory tract, and on the skin. Although approximately 30% of the human population has S. aureus living in or on them, during times of immune suppression, S. aureus can cause skin and blood infections. Without antibiotic treatment, S. aureus bacteremia (bloodstream infection) has a fatality rate that ranges from 15 to 50 percent. Unfortunately, the prevalence of S. aureus in antimicrobial filled hospitals has lead the species to be highly resistant to many drugs. For example, MRSA is methicillin-resistant S. aureus, a highly difficult bacterium to treat. Many S. aureus strains are now classified as MDRO, as they are resistant to more drugs than just methicillin. Without novel antimicrobials to treat S. aureus infections, or any other MDRO infection, the fatality rates will only increase.

S. aureus is in the genus Staphylococcus and has many other genus family members, many of whom also live in the human nose. The authors of this study used a previously described collection of nasal Staphylococcus to screen the species’ ability to inhibit the growth of S. aureus. They identified one strain, called S. lugdunensis IVK28, which very strongly prevented the growth of S. aureus. In the hopes of identifying the specific molecule, or molecules, that S. lugdunensis uses as an antimicrobial against S. aureus, which could subsequently be used as clinical antimicrobials, the authors made a mutant library of S. lugdenensis. In essence, this means that they modified the entirety of the genome of S. lugdenensis randomly in many different ways. If a gene is mutated that is critical to repressing S. aureus growth, then that mutant would be unable prevent S. aureus growth. Then, they tested to see if any of the mutants were unable to repress S. aureus growth. When they found one mutant that did not have this antimicrobial property, they sequenced the bacteria’s genome to identify what gene was mutated. They found that the previously uncharacterized gene, which they named lugdunin, was mutated in this line of S. lugdunensis. This is the first clue showing that lugdunin could be a novel antimicrobial.

To test if lugdunin has antimicrobial properties outside of the context of S. lugdunensis, the authors isolated lugdunin on its own and found that it was able to independently act as an antimicrobial on S. aureus growth. This fact is important in that many molecules, particularly proteins, sometimes don’t function alone, working in conjunction with other proteins, or other biomolecules such as lipids or nucleic acids. An independently functioning molecule is much easier to work with, both in basic science characterization studies, as well as in the clinic. Lugdunin is a strong antimicrobial, with the ability to act against various strains of drug-resistant S. aureus and drug-resistant members of the Enterococcus genus, as well as many other bacteria. Importantly, lugdunin did not cause any damage to human cells (important when trying to develop a drug for human use). When the authors used a mouse skin infection model using S. aureus, lugdunin was able to eliminate most or all of the infection, a first critical experiment in demonstrating its potential as a clinically available antimicrobial.
The question of why some people are carriers of S. aureus, while others may go their entire lives without have one such bacterium ever live in or on them, has remained largely unanswered by scientists. To explore whether the presence of S. lugdunensis affects the presence of S. aureus, 187 patients’ nasal swabs were analyzed. A third of the patients had S. aureus, a number close to the national average, whereas a tenth of the patients had S. lugdunensis. The presence of S. lugdunensis, however, strongly decreased the likelihood that the patient had S. aureus. Although it couldn’t definitively be proved in humans, as human testing is strictly frowned upon by the higher powers that be in the scientific world, this finding was a critical step in understanding the relationship between the two Staphylococcus strains.

To further test this antagonized relationship, the authors asked whether lugdunin gave S. lugdunensis the capacity to outcompete S. aureus for nasal space. They found that this, in fact, is true. When they plated both bacteria on agar plates (basically thick jello with tons of nutrients), they found that S. lugdunensis always took over the plates within 72 hours. Even when the plate started as 90% aureus and 10% lugdunensis, three days later, there wasn’t a S. aureus bacterium to be found. When a mutated S. lugdunensis was used, a variant that lacked the lugdunin, S. aureus was able to take over the plate with ease. These findings show that S. lugdunensis is not just a member of many people’s nasal microbiota, but its ability to compete with S. aureus, thanks to its lugdunin molecule, can keep aureus at bay and prevent any potential infections it would cause.

The discovery of a potent antimicrobial that can act on drug-resistant bacteria is important. Of course, there is always the risk that bacteria will develop a resistance to this new antimicrobial, but when the authors of this study tested to see whether they can ‘force’ S. aureus to become lugdunin-resistant, they found that the rate of resistance development was minimal. Whereas S. aureus developed resistance to other drugs after even just a few days, lugdunin resistance wasn’t observed, even after a month. Lugdunin is an exciting new antimicrobial that hopefully will be able to treated MDRO-infected individuals soon. Additionally, as S. lugdunensis is a known safe nasal commensal, a fascinating potential of these findings is infection prevention, instead of treatment. Patients who are at a high risk for S. aureus infection can be colonized with S. lugdunenesis to make the bacteria work for us in exchange for the delicious mucus they feast on. The presence of this S. aureus fighter will lower the risk for S. aureus presence, even already drug-resistant S. aureus, in the nasal cavity, lowering the chance of a life threatening infection. Although it was a quiet field for a while, antimicrobial discovery has only been speeding up in the last few years. Exciting new discoveries are being published every few weeks and our ability to treat infections, as well as preventing them in the first place, is only getting better. Who knew that sharing boogers could save lives?


The Parasite Manipulation Hypothesis: How To Get Where You Need To Be

By: Helen Beilinson

           In 1990, after students proposed a project asking whether frogs can hop in zero gravity, six Japanese tree frogs went to space. This question, as well as many others, was answered in the “frog in space” experiment (FRIS) of the early 1990’s. Two decades later, the mating calls of male Japanese tree frogs were the inspiration for an algorithm to create efficient wireless networks. Recently, these frogs, and their mating calls, have made it into the news again when a group from Korea showed that when these male frogs are infected with the fungus Batrachochytrium dendrobatidis, their mating calls become ‘sexier’.

            B. dendrobatidis infects various amphibian species, including the Japanese tree frog. This fungus causes a wide range of changes to the bodies of its host, including electrolyte and fluid imbalance, leading to heart failure and rapid death of immune cells. While some amphibians are susceptible to B. dendrobatidis and will die when infected, some, including the Japanese tree frog, are not. The Japanese tree frog is tolerant to the infection, meaning that after being infected, instead of destroying the pathogen (this occurs in resistant hosts), the pathogen remains within the host, but does not cause significant damage to the host (as occurs in susceptible hosts). Interestingly, even though no detectable changes occur in infected male Japanese tree frogs, other than very slight weight gain and lethargy, their mating calls change.

            After collecting and analyzing mating calls from male Japanese tree frogs, the authors found that those frogs infected with B. dendrobatidis had calls that made them more attractive to females. The scientists analyzed the calls for number of pulses per note, the repetition rate of the pulses, the number of notes, and the duration of the calls. The infected males’ calls were faster and longer, traits female frogs are known to find more attractive. The fungus and the tree frogs have evolved a relationship that presumably increases the fungus’ ability to spread, as the more females their host interacts with as a result of their more sultry call, the more new hosts the fungus can spread to.

            The manipulation of host behavior by fungi and other parasites in order to facilitate transmission to new hosts is not a new idea. The ‘parasite manipulation hypothesis’, first described in the early twentieth century, describes this phenomenon in which parasites purposefully alter the behavior of their host to increase the probability that they interact with a new potential host. A well-known example of such a parasite is Toxoplasma gondii, a protozoan that infects a broad spectrum of warm-blooded animals.

            T. gondii is a protozoan (a unicellular eukaryotic organism) whose life cycle has two components. The first is asexual, where it replicates by fission, and can happen in almost all warm-blooded species. The second is sexual, where two individual T. gondii ‘mate’ to form genetically different progeny, and only can occur in feline species’ intestinal cells. Famously, mice infected with T. gondii no longer have an innate aversion for cat urine odor, making them more likely to be caught, and eaten, by cats. It is thought that this behavior change makes it easier for T. gondii to spread to cats, their preferred host and the only host in which they can sexually replicate (sexual reproduction is preferred because it increases the genetic diversity of the species). Humans can also be a host for T. gondii; in fact, it’s one of the most common parasites in the western world, with nearly half of the population being infected. Fortunately, the infection does not seem to induce disease (toxoplasmosis) unless the infected human is immunocompromised (like infants, AIDS patients, and patients on chemotherapy). However, there are some interesting correlation studies showing that infected human men no longer find the smell of cat urine unpleasant.

            Humans are not a good intermediate host for T. gondii to infect, because we no longer have natural feline predators. Chimpanzees, however, have one known feline predator… the leopard. When scientists studied the influence of T. gondii infection on chimpanzee behavior, they found similar results as has been noted for years in mice: infected chimps lost their innate aversion to leopard urine. Presumably, the protozoan induces this phenomenon to increase the probability that its chimpanzee host is predated by leopards, such that the protozoan can replicate in the leopard. Interestingly, when the scientists studied the chimps’ attraction or aversion to another feline’s urine compared to leopard urine, they found that the affect of T. gondii only affected the chimps’ attraction to leopard urine, not lion urine. This result indicates that the lack of aversion to urine induced by T. gondii in chimps is specific to the urine of felines residing in proximity to their hosts. Additionally, in the previous study mentioned where infected human men do not find cat urine unpleasant, they still found tiger urine to have an irksome smell. The studies done in T. gondii infected chimps and humans were correlative, but they do produce stimulating evidence for the parasite manipulation hypothesis.

            B. dendrobatidis and T. gondii are nowhere near the only parasites able to manipulate the behavior of their hosts. A tapeworm infection in stickleback fish, native to cold saltwater regions, and malaria infection in female great tits, a common bird species in Europe, Central Asia, and North Africa, causes the species more bold in exploring new territories, making them more susceptible to predation. In humans, parasite manipulation may not be of concern, as we are no longer prey to other animals, but it is a predominant effect in the animal world. Not only does this effect point to the incredibly intricate relationships that are formed between host and parasite, but also show the importance of innate animal behaviors keeping them away from potentially dangerous situations.