Wednesday, November 30, 2016

Further down the trail....Mary has died of typhoid

"Mary has died of typhoid." Yet another disease you may remember encountering on The Oregon Trail in childhood, typhoid fever, or simply typhoid, is also still a major public health concern today. Affecting an estimated 20.6 million people and causing 223,000 deaths a year, typhoid is caused by the bacterium Salmonella enterica serovar Typhi (S. Typhi). The bacteria is often spread through contaminated water or from person-to-person contact. In places where clean water and sanitation are standard, the disease has been essentially eliminated. But in developing countries, it remains a major threat.

The most recent outbreak of typhoid occurred just last week in the city of Masvingo, Zimbabwe. Areas where the disease is endemic and can lead to outbreaks include Southeast Asia, Africa, and South America.  Travel to and from these areas also allows for the transmission of the bacteria to industrialized nations and can cause local outbreaks. Although there are currently two approved vaccines against S. Typhi, both have drawbacks that prevent them from being used en masse. The protective efficacy of the vaccines is sub-optimal and ranges from 40%-70%, largely dependent upon age and location. Additionally, the protection from the vaccines is short-lived, averaging 2-3 years for one vaccine and 5-7 years for the other. A further complication is that both vaccines need to be stored with refrigeration until they are used. Transport and storage under these conditions are major difficulties in countries where electricity is a supreme luxury.

Without a reliable vaccine, the major way to fight the disease is through the use of antibiotics. Chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole, very common antibiotics, have historically been used to stop the infection, and this strategy was highly successful for many years. However, in recent years, a new threat has emerged to thwart these efforts. In the 1970s, cases of S. Typhi that were resistant to these antibiotics began to emerge. We now face the threat of multi-drug resistant S. Typhi, making disease treatment much more difficult.

In light of the rising drug resistance, many have begun to see wide-spread vaccination as the best strategy to fight typhoid. Others argue that improving water sanitation will have the greatest effect on decreasing disease prevalence. One thing is certain: either strategy will require a large investment of funds to be achieved.

The Bill & Melinda Gates Foundation is leading the way in the funding arena and has identified the elimination of typhoid as a public health problem by 2035 as a goal. The Gates Foundation recently gave over half a million dollars to Yale University to explore and determine the cost-effectiveness of typhoid vaccination strategies. Additionally, The Gates Foundation gave a $36.9 million grant earlier this month to a collaboration between the Maryland School of Medicine Center for Vaccine Development, the Oxford Vaccine Group, and PATH, a non-profit public health organization, to accelerate the development of a new vaccine to be used in young children. The goal is to develop a vaccine with more long-lasting protection than the two currently available. The Gates Foundation is also providing funds to increase surveillance for typhoid in South Asia and Africa.

While the Gates Foundation is leading the way to fund the vaccination strategy, other groups are focusing on improving water sanitation. The United States Agency for International Development (USAID) features water and sanitation as one of its main avenues of focus, with sponsored projects underway in large portions of Africa and Southeast Asia. The World Bank has also been sponsoring projects to improve water quality and health throughout the world. Additionally, UNICEF has been a major player in the increased access to clean water that has over the past decade. Many other smaller non-profits have also played a role in this endeavor.

As both vaccine and water and sanitation improvements occur, our ability to battle this age-old pathogen will increase. Using both strategies simultaneously allows for the most rapid and sustainable progress toward S. Typhi elimination. With the continued investment of groups like the Gates Foundation and USAID, the goal of typhoid elimination as a public health problem by 2035 might just be achievable.

Sunday, October 30, 2016

Cholera: Not just a problem on The Oregon Trail

"Sally has died of cholera." This was a common problem in the game The Oregon Trail that many people remember from childhood. Tragically, cholera is still a major public health problem in countries around the world today. Cholera is caused by the bacterium Vibrio cholerae, which is shed in fecal matter from an infected individual and is often transmitted via contamination of water sources. In countries with poor sanitation and a lack of clean water, this can lead to significant and deadly outbreaks.

Fast-forward from the days of the Oregon Trail to present-day Haiti. The country has suffered multiple tragedies in recent years. In 2010, they were rocked with a devastating earthquake; now, in 2016, they suffered the wrath of Hurricane Matthew. In light of these recent disasters, there have been humanitarian efforts from the United Nations and other relief organizations. Unfortunately, in the wake of the U.N.'s help after the 2010 earthquake, Haiti experienced its first cholera outbreak.

Before 2010, the small nation of Haiti had not been exposed to cholera. The citizens had not had the disease, and no immunity to the pathogen existed there. The first case of cholera was reported in mid-October 2010 in the region of the country along the Meille River. The disease quickly became rampant, with a hospital 60 miles away from the first case reporting new cases every 3.5 minutes within just 2 days. Since then, the outbreak has affected nearly 800,000 people and caused more than 9,000 deaths according to the official numbers; however, many experts fear the true impact has been far greater due to poor case reporting.

Flooding and destruction from Hurricane Matthew on October 4, 2016, have done nothing to help the situation. As many Haitians have lost their homes and their sources of fresh water, cholera has been on the rise again. Flooding has led to increases in contaminated waterways, leaving much of the water unsafe for consumption. Within four days of the storm passing through, officials were reporting 62 cases and 13 deaths from cholera.

The issue of how cholera came to be endemic in Haiti has been a topic of heated debate in the past few years. Many have blamed the U.N.'s Nepalese peacekeeping troops for bringing the bacteria with them into the country following the 2010 earthquake. The U.N. has denied any potential responsibility for the outbreak for years, even in the face of lawsuits from families of those who had died. Others hypothesized that increases in the temperature and salinity of the rivers throughout Haiti had allowed bacteria that may have been living in a dormant state in coastal waters to populate these rivers after the earthquake.

Scientific evidence, however, has been on the side of those who blame the U.N.'s peacekeeping troops for the introduction of the disease. Genetic analyses by whole genome sequencing of the bacteria found in Haiti in 2010 showed that this strain was highly similar to the strain found in Nepal in 2010. Additional studies using multiple-locus variable number tandem repeat analysis (aka DNA fingerprinting), a technique that looks at the number of times a DNA sequence is repeated at specific loci in the genome, also suggested a match between the Nepalese and Haitian strains.

On August 18, 2016, after 6 years of denial, the U.N. finally acknowledged that they did play a role in the initial outbreak. Farhan Haq, the deputy spokesman for the U.N. secretary general, said "over the past year, the U.N. has become convinced that it needs to do much more regarding its own involvement in the initial outbreak and the suffering of those affected by cholera...[a] new response will be presented publicly within the next two months."

The latest chapter in this story comes with the announcement on October 24 that the U.N. is working on a plan to spend about $400 million on cholera in Haiti. Roughly $200 million will be spent on cholera elimination efforts, while the other $200 million will be given directly to families or communities affected by the disease. The full details of the plan are expected to be solidified in the coming weeks. However, questions remain over how the money for this plan will materialize. U.N. member states have already expressed discomfort with paying money to directly compensate victims, as this is not within the purview of the normal development work the U.N. is chartered to perform.

While the final details of the U.N.'s action plan remain to be worked out, it looks like Haiti will be receiving some much-needed support to aid in their cholera elimination efforts in the near future. As the country rebuilds after Hurricane Matthew, water sanitation will be a major focus for the nation. With financial support and help from the U.N., experts are hopeful that cholera can be eliminated fairly quickly from Haiti. That would serve as a major beacon of hope for a nation that has borne the brunt of tragedies for too long.

Friday, September 30, 2016

The not-so-loving kissing bug

As fall approaches and the weather begins to cool from the stifling heat of summer, we all like to spend a bit more time outside enjoying the air. Unfortunately, this is the perfect time for insects who like to feed on our blood and potentially carry disease to come out and join us. Most people think of ticks and mosquitoes when they think of insects that carry disease, but there is another major player in the Americas: the Triatominae, also known as the kissing bug. This little creature can carry a parasite known as Trypanosoma cruzi, which causes Chagas disease.

Image result for the kissing bug
The Triatominae insect, aka the kissing bug, that
can carry the Trypanosoma cruzi parasite that
causes Chagas disease.
Image from Snopes.com
Chagas disease is a major global health threat, with 70 million people at risk of exposure and approximately 5.7 million people becoming infected each year. The disease mainly affects Latin America, but thanks to population flows and increases in vector populations, the disease has been spreading to the north, with cases reported in the US in Texas, in Canada, and even in Europe. The disease exists in two phases, the acute phase and the chronic phase. During acute infection, there are large numbers of parasites in the blood, but symptoms are few and non-specific. There can be fever, headache, swollen lymph nodes, or even completely asymptomatic cases. As the disease transitions into the chronic phase, the parasites sequester into the muscle of the heart and digestive tract. This can result in severe cardiac and digestive disorders, which can last for years after the original infection began. Most dangerously, heart failure can result, causing death.

Treatment for Chagas disease remains a major issue. There are very effective treatments for the acute phase, with almost 100% efficacy, but these treatments are underutilized. Treatment requires rapid diagnosis of the disease, which is often difficult due to the non-descript or non-existent symptoms. Also, the drugs need to be administered over a very long duration, 60-90 days, leading to low follow-through rates for treatment to completion. Unfortunately, there are currently no treatments for the chronic phase.

Current work being done at the University of Georgia is working to address one of these problems. They are focused on developing affordable diagnostic tests that can be used anywhere to diagnose Chagas disease in the acute phase. Their efforts focus on increasing the number of T. cruzi antibodies being detected in the test in order to allow for a more sensitive test. Not only will the test help identify people who have the disease, but it will also improve the ability to monitor how well a person is responding to treatment, hopefully allowing for decreases in treatment times.

Beyond the work at the University of Georgia focusing on improving diagnostics, there has also been a lot of effort into developing new treatments for Chagas disease. The Drugs for Neglected Diseases Initiative has chosen Chagas as one of their focus diseases and has been working on new therapeutics to treat both the acute and chronic phases of disease. Their goal is to develop an orally administrated treatment that will require less than 30 days of administration by 2020. They have moved into a Phase II proof of concept study with two different treatment options, with results expected late this year and early next year.

While advances are being made in detection and treatment of Chagas in humans, there are also many animals that are threatened by this disease. Chagas disease can also affect both wild and domestic animals, making elimination of the parasite reservoir impossible. Notably, Chagas disease in dogs is known to be frequently fatal, causing the same heart failure and cardiac symptoms seen in humans with chronic Chagas disease. For dogs, there is currently no available treatment for the disease. 

The best way to deal with Chagas for the time being is the prevent it. Insecticide spraying is encouraged by the World Health Organization and has been shown to decrease the incidence of disease. Also, being able to identify the Triatominae insects when they are seen can help people avoid areas where they could become susceptible to being bitten. These bugs are known to enjoy living in hay, woodpiles, and under porches, so avoiding these areas can help reduce transmission of the parasite. 

To protect yourself and your furry friends this fall, be sure to be on the lookout for the kissing bug. One kiss from this little love bug may just be your worst first date ever.  

Tuesday, August 16, 2016

Amanda Elmore and Team USA's victory in the Olympic W8+ is cause for excitement, but the health risks they faced to achieve this feat are not

Rio de Janeiro. Already well known for its vibrant culture and nightlife, this Brazilian city has also become known for sports this month as they play host to the Games of the 31st Olympiad. Many brand new athletic facilities were created specifically for these games, and Brazil poured a projected $18 billion or more into bringing these games to life. Even more funding was supplied by sponsors, like Coca Cola. Unfortunately, not all sports venues could be made ideal.

Guanabara Bay and Copacabana Beach off the coast of Rio are the sites of five aquatic events in this year's games: sailing, rowing, canoe sprinting, the triathlon, and marathon swimming. In addition to hosting these great sporting events, these waterways also play host to many unwelcome guests: multi-drug resistant bacteria and viruses of many varieties.

The Brazilian government has been aware for years that raw sewage has rushed into their waterways from the cities. In their bid to bring the Olympics to Rio, Brazil pledged to put forth $4 billion to deal with their water contamination issues. Unfortunately, due to a "budget crisis" they were only able to invest $170 million before the Games began. The results of this lack of funding may end up having devastating effects on the health of athletes at these games.

A study published by Renata Cristina Picao's group in Brazil in 2015 looked specifically at the bacterial populations of the water from the beaches surrounding Rio de Janeiro. They studied a total of 18 water samples from different regions along the coastline. Of these isolates, only one had bacteria with susceptibility to imipenem, a common drug used to treat bacterial infections in this area. Resistance rates to other popular drugs were also alarmingly high, with 77.8% of the isolates showing bacteria with resistance to cefotaxime, 50% showing resistance to cefepime, 27.8% showing resistance to gentamicin and amikacin, and 5.6% showing resistance to ciprofloxacin. With drug resistance running rampant in the bacteria that call this water home, being on or, even worse, in this water may pose a significant health threat to athletes.

Possibly an even larger threat than the bacteria in these waters are the viruses that can also be found. Hepatitis A virus can be found in human waste, and experts speculate that ~60% of Brazilian adults are exposed to the virus. In waters that contain large amounts of human waste, like the ones the athletes will be exposed to, the risk of infection is significant. The CDC recommends that all travelers to Brazil, not just those who will be exposed to the water, receive the Hepatitis A vaccine. With appropriate use of the vaccine, an outbreak of Hepatitis A can likely be prevented, though some have questioned whether or not the vaccine will protect against the local strains of the virus.

In addition to Hepatitis A virus, water tests have found alarmingly high levels of multiple types of adenovirus, which can cause severe gastrointestinal problems and do not have vaccines. Fernando Spilki, a Brazilian virologist, performed water testing for the Associated Press and found levels of adenovirus from 14 million to 1.7 billion virions per liter of water. To put this in perspective, California officials become concerned about their water quality if the level rises to just 1,000 virions per liter.

Many may wonder why, with the popularity of these beaches among Brazilians, there has not been a major viral outbreak or an outbreak of multi-drug resistant bacteria in the region already. The answer likely lies in the fact that these native-born and raised Brazilians have been exposed to these bacteria and viruses from a very young age, allowing their bodies to develop a successful immune response to the pathogens. However, the same immunity will not exist for the foreign athletes who will be exposed to these waters.

In the year leading up to these games, some athletic groups have already trained and raced on these waters. Many documented athletes experiencing illness. The World Junior Rowing Championships were held in Rio in 2015, and the U.S. team documented 13 rowers who suffered gastrointestinal illness following the event. The Australian sailing team has trained on the waters around Rio for the past several months, and they also have had athletes fall ill with gastrointestinal problems.

Though independent water testing has identified the water as potentially hazardous to health, the International Olympic Committee has maintained that the water is safe enough for the events to be held. The World Health Organization (WHO) has recognized that the water quality is less-than-ideal, and has issued several statements for travelers warning them of the potential for infection if exposure to contaminated water occurs. Additionally, the WHO has recognized that sites in the Guanabarra Bay, where sailing, rowing, and canoe sprinting take place, do not always meet the standards of safety, based on bacterial testing. As a precaution, they recommend that for all bodies of water "all athletes should cover cuts and grazes with waterproof plasters prior to exposure, try to avoid swallowing the water, wash/shower as soon as possible after exposure and, as far as possible, minimize their time in the water and avoid going in the water after heavy rainfall if possible." In events like the triathlon, where the swim portion is upwards of 20 minutes, and the marathon swim, which can take 2 hours or more to complete, minimizing time in the water is not always a viable option.

In light of the potential health risks, athletes and spectators alike will need to use increased caution regarding the Rio games. Monitoring for illness is going to be critical to prevent severe illnesses from developing. Many have focused on the potential threat of Zika virus at these games, but the threat of the multi-drug resistant bacteria and viruses in the waters should not be forgotten. All can cause significant problems and really ruin the Olympic experience. Perhaps next time the Olympic Committee will be more skeptical of selecting a location with such serious health concerns unless they are willing to chip in some funds to help the country address the situation. Such a gesture would not only have a positive impact on the athletes, but more importantly, it would have a sustained impact on the residents of the host country for years after the conclusion of the Games.


--On a side note, I'm so proud of my former teammate Amanda Elmore and the entire U.S. W8+ for dominating and winning gold at Rio!! Boiler Up!

Wednesday, July 20, 2016

Pitfalls of some big-name institutions to avoid

Note: This article describes my observations at particular institutions and is not meant to be a generalization of all places, though certain themes, I'm sure, are wide-spread.

Many researchers want to work for a big-name institution. They get the best perks, get the most recognition, and can provide the best resources to employees. However, there are often problems at big-name institutions. Egos the size of dinosaurs fill the halls, and the power-hungry dominate the meeting rooms. In this type of culture, success can seem impossible. In this particular piece, I plan to highlight some of issues that arise in this type of environment, told from my own perspective.

Student entitlement
"I got into this institution, so everyone should be working for my success."
Students can come into these types of institutions with a strong feeling of entitlement. They think that getting into a good school means they will automatically succeed; and, if they aren't succeeding, it must clearly be someone else's fault. Often times, these students turn the professors into scapegoats for their failings. "That prof grades unfairly." "This prof is too demanding of students." "My thesis adviser isn't ok with me just working from 10-3 every day." These are just some of the complaints I've heard. It's never, "I should have studied harder," or "I should have put in more time." Some students are willing to take pretty extreme measures to push their agenda, such as raising an official complaint against a faculty member. And even when an impartial committee hears the case and rules in favor of the faculty member, the student may still continue to hold onto their delusional notion that the faculty member is out to get students. Just one student can do serious damage to a faculty member's reputation.
From the point of view of faculty, there are really two ways to respond to this culture. You can either lower your standards to accommodate the students who refuse to rise up, or you can continue to keep the bar high and let them hate you. It may seem like it would be fairly easy to take the high road and deal with being unliked by the students, but there are some serious consequences to consider here. When other faculty chose to lower their standards and you don't, your department starts viewing you as an outsider. You will be the one member of every thesis committee who is saying, "This person shouldn't be graduating yet," and other faculty can view you as difficult. Additionally, students will no longer chose to work in your lab based on the negative comments from older students, making it very difficult and more expensive to get research done (post-docs will soon make more than twice the salary of a typical PhD student in most institutions thanks to new legislation). This can be too high a price to pay for many faculty.

Big egos cause big problems
A single room can only hold so much ego before it bursts. At top-tier institutions, there can often be the problem of too much ego for one room to hold. This can lead to passive-aggressive shoving matches fought behind closed doors or all-out shouting battles. This is especially problematic, it seems, in the case of older faculty versus younger faculty. Many older faculty feel very secure in their role at the top of the food chain, thanks to their long track record of professorship. When a young faculty member comes in and brings lots of success quickly, alarm bells go off. The older faculty must now assert their dominance to make sure the younger faculty stays below them on the totem pole. This can mean passing people over for promotions they deserve, intentionally withholding departmental grants from a faculty member or their students, or even using your influence to direct good students and post-docs away from a particular lab.

Money runs the game
"You've heard of the golden rule, haven't you? Whoever has the gold makes the rules." Jafar speaks this classic line in Disney's Aladdin, but it holds true in many situations. Grant money runs the scientific environment, and in the current times of funding shortages, this form of the golden rule has never been more accurate. Labs with funding are able to recruit the "best" post-doctoral fellows and students, while poorly funded labs struggle to bring in much talent. This can be a self-perpetuating cycle. Also, oftentimes, well funded labs do not feel the need to collaborate as much, because they can get things done by themselves. This leaves little room for an up-and-coming lab to break into the system.

Who you know matters...a lot
Why is it that the students from the same labs always win certain awards, or certain labs are always able to get their work into that coveted journal? Sometimes it's because the lab is just that good, and produces superior work over and over again. Sometimes, though, it's because of the politics. Science can be a big game of who you know and what alliances you make. Knowing the right people can go a long way towards boosting scientific success, or at least perceived success in the form of awards or papers in good journals. However, this does not always align with the quality of the work, so "working the system" can catapult researchers to the fore-front of attention ahead of some who do good work, but are less well-connected.

Competition trumps collaboration
The hallmark of a successful scientific institution is often its collaborative environment. Unfortunately, some of the top-tier places lack this feeling. With so many high-powered research groups in one place, it's hard not to feel potentially threatened by your neighbor down the hall. This leads to the strategic withholding of information, omission of key details from departmental meetings, and protocol secrecy. The end result: researchers wasting time optimizing protocols someone next door has already optimized, students worrying that their work is going to be constantly scooped, and people not reaching out for help when they need it. This ultimately slows down the scientific process, not to mention wastes valuable financial resources.

Don't let the door hit you on the way out
Since competition can be so strong at top-tier institutions, when a faculty member that others perceive as a potential threat to their research prowess leaves, others may be far too ready to let them go. Each faculty brings unique skills and insights to a department, but many departments are ready to throw away faculty without a second thought if they feel threatened. The collaborative environment that needs to exist in science is especially threatened by this type of attitude.

Take some advice from Tim McGraw
"Don't take for granted the love this life gives you; when you get where you're goin', don't forget turn back around; and help the next one in line; always stay humble and kind."
Tim McGraw's recent song seems to be speaking a message directly to these top-tier institutions with these words. In a world of competition and surrounded by your own successes, it can be difficult to stay humble and kind. But that's exactly what we need in these institutions to maintain the collaborative spirit and culture of science for the sake of science (and not success) that is essential for improvements in the world. So, please, the next time "the work you put in is realized, let yourself feel the pride but always stay humble and kind."

Monday, July 18, 2016

The wonders of the biofilm world

What do you moving your arm and a biofilm of bacteria growing have in common? The answer is more than you might think. You moving your arm involves the propagation of an action potential through neurons that connect your brain with your limbs. This action potential is based on the rapid movement of ions into and out of cells, allowing each cell to pass a message on to the cell next to it through these ions. As the charged ions flux in and out of cells, the membrane potential (or chemical voltage) of the cells changes. It turns out that biofilm bacteria can use a similar system in order to communicate.

from Anatomy & Physiology by Phil Schatz
Action potentials have long been known as a rapid way to propagate signals over long distances. As ion channels open or close over the course of the action potential, the charged particles flow in and out of the cell in response to their concentration gradients. This is what allows the changes in membrane potential within the cells. But it has only recently been found that Eukaryotes are not the only organisms that can do this.

Enter Bacillus subtilis, a bacterium often used as a model organism for studying biofilms. A biofilm is a collection of bacteria that adhere to each other and, often, a surface. Biofilms are more resistant to antibiotic treatment than free-living bacteria, and can commonly be formed on medical devices, such as catheters. It has been known for many years that bacteria within a biofilm are able to communicate through a process known as quorum sensing, which involves the release of chemicals by the members of the biofilm to control the population density. Recently, a study found that in addition to quorum sensing, B. subtilis cells can communicate through the creation of and propagation of action potentials, similar to neuronal signaling.

It was observed that the entirety of the B. subtilis biofilm would undergo metabolic changes in response to glutamate and ammonium nutrient limitation affecting the cells in the center of the biofilm. In order for these widespread metabolic changes to occur, the cells in the interior of the biofilm must communicate with the cells of the periphery. It was found that an active propagation of a potassium ion signal through the use of potassium channels on the cells was responsible for this communication. As the potassium channels on the surface of the bacteria opened, potassium would rush into the cells from the surrounding environment, resulting in membrane depolarization. The membrane depolarization is linked to a decreased ability of the cells to take up glutamate and ammonium, allowing these nutrients to build up and replenish the supply to the interior cells.

Biofilms are notoriously difficult to treat when they form in patients. As many as 80% of chronic infections are caused by biofilm formation. Persistent staphylococcal infections are often caused by biofilms, as are Pseudomonas aeruginosa lung infections. It is typically the interior cells of the biofilm, which have a more dormant lifestyle, that are most responsible for antibiotic resistance. Learning more about how the biofilms communicate can facilitate improved treatment. If the action potential creation of these bacteria can be inhibited, the cells will be unable to communicate in times of nutrient depletion, leading the cell death at the interior of the biofilm. This could greatly improve the ability to treat these infections, leading to better outcomes for patients. Perhaps some day soon, we will have better tools for treatment to gain ground against these crafty biofilm bacteria.

Beyond the impact of these findings on patients, it is truly marvelous to see what these relatively simple organisms can accomplish. Bacterial cells are almost 1000 times simpler than mammalian cells when genome sizes are compared, yet they are capable of accomplishing signaling akin to the complexity of neuronal signaling. There seems to be no end to the surprises these timeless organisms have in store for us. Who knows what will come to light next.

Friday, July 1, 2016

Where did June go?

Hello world,
I realized last night as I was trying to go to sleep that I was going to fail at getting a June blog post up in time. I've been working on two different pieces, but neither of them felt ready to post. That's why this month (July), I'll be posting three (yes, that's right, THREE) different pieces. Expect to see those in the fourth week of the month. Until then, I am condemned to a life of boxes and packing as my lab and I prepare to move to Florida. See you when this process ends.