Malaria and foot odor-the missing link!

Via Gawker.com and the LA Times, here’s a news alert that all college students should be mindful of. Researchers at the London School of Hygiene and Tropical Medicine have published in the medical journal PLOS One a new defense against malaria transmission. Malaria is a disease which affects a large proportion of the world’s population, with an estimated 220 million cases (nearly 1 in 20 people) worldwide in 2010. It is caused by the several species of the protozoan genus Plasmodium, and transmission requires specific species of mosquitoes that are essential for the life cycle of Plasmodium. There are treatments for malaria that can help infected patients to clear the parasite, but there is currently no vaccine. Main methods for control for the transmission of malaria have traditionally focused on controlling the reproduction of mosquitoes.

The experiments conducted by the researchers were simple; new adult female mosquitoes were fed human blood which was either infected or uninfected with Plasmodium. Following verification of infection, mosquitoes were introduced to socks (20 Den panty sock, HEMA, The Netherlands) that had been worn for 20 hours beforehand

…by a male volunteer of whom the relative attractiveness to An. gambiae s.s. compared to 47 other men is known…

Control socks, of course, were fresh right out of the package. The researchers constructed a mesh matrix, and measured the rate at which the mosquitoes landed on the matrix (landing rate).

As can be clearly noted from their data figure, infected mosquitoes were 4 times as likely to be attracted to the human odor than uninfected mosquitoes. The authors conclude that the presence of Plasmodium is altering the behavior of the mosquitoes, which may increase the rate of transmission as the population of infected vectors (the mosquitoes) rises. They suggest that current mathematical models for malaria transmission may be underestimating the rate at which the protozoan spreads through populations, as generally uninfected mosquitoes are used in behavioral studies and do not take into account the effects of the parasites themselves on vector-host interactions. Effective malaria control programs need to accurately model all aspects of parasite/vector/host interactions.

From the point of view of the pathogen (Plasmodium,) this is a perfect strategy. Plasmodium species depend upon the mosquito vector for the sexual portion of their life cycle, and this requires approximately 2 to 3 weeks to occur. As this occurs, it is advantageous for the organism not to be transmitted to a new host during a blood meal. However, after sexual maturation has occurred and the new sporozoites migrate to the salivary glands of the mosquito, modification of behavior will allow the subsequent transmission back into a new host during as the mosquito feeds. Long time fans of BIO230 will recall how another Apicomplexan protozoan, Toxoplasma gondii, has been found to potentially modify its host’s behavior, leading to the inappropriately named “Crazy Cat Lady Syndrome.”

Synergism in action: co-infection of a yeast and a bacterium

C. albicans (pink) in murine kidney. Image copyright D. Singleton, YCP

An article in the latest issue of Infection and Immunity caught my attention: “Candida albicans-Staphylococcus aureus Polymicrobial Peritonitis Modulates Host Innate Immunity” describes work by researchers at the Louisiana State University Health Science Center. Many models of infectious disease use virulence studies in animals such as mice. A typical experiment may infect an animal with a defined number of pathogenic organisms, and changes in health of the animal are measured–this is the basic premise of Koch’s Postulates, where the etiologic agent of a disease can be experimentally determined. Some diseases of humans may not be well mimicked in animal models, and this presents a problem when trying to study significant human diseases.

The work summarized here examined the disease produced by two separate pathogens, the Gram positive bacterium Staphylococcus aureus, and the fungus Candida albicans. Infection of mice with either one of these pathogens was non lethal at the infectious doses used in their experiments. However, when an animal was co-infected with both the bacterium and the fungus at the same time and at the same individual dose, a 40% mortality rate was observed, with significant infiltration of the organisms into the peritoneum and other target organs. At the same time, a number of important immune system signalling hormones were also elevated in mice who were co-infected with both pathogens, leading to a much higher inflammatory response in those animals. Mice treated at the same time with the inflammation inhibitor indomethacin did not die. Further injection of mice with a second inflammatory medidator prostaglandin E2 at the same time as administering indomethacin overrode the protective effects of indomethacin, and significant mortality of mice was again observed. The authors conclude that combination of pathogens have very important effects on the innate immune response, and that the lethality of the disease is exacerbated by the powerful inflammatory response.

Nosocomial infections are a critical issue in US health care, with billions of dollars annually being adding to the total costs of our health care. The graphic to the left from our textbook illustrates the relative contributions of various classes of pathogens; the sections of the pie labeled “Gram-positive bacteria” and “Yeast” are comprised primarily of the two species in this report, S. aureus and C. albicans. Many of the organisms responsible for causing nosocomial infections do so due to the a perfect storm of conditions in health care–a population very susceptible individuals, healthy carriers moving between patients, use of antibiotics leading to resistance, medical procedures which can bypass normal routes of entry for these pathogens. The first inclination upon developing a nosocomial infection is to combat it with antibiotics, and in fact many surgical procedures may involve the prophylactic use of antibiotics to help avoid this outcome. But the use of antibiotics themselves can lead to problems in the form of rampant antibiotic resistance and loss of efficacy of those drugs. This research shows that an alternative approach that tweaks the host’s immune response might also be effective.

Can R2D2 Beat H1N1?

Constance Heidel (3 PM Micro) was fascinated by the threat of antimicrobial resistance, and our ongoing efforts in to try and combat this potential health care disaster. Here is Constance’s take on a way that hospitals are currently trying to eliminate these microorganisms from clinical settings:

 

As a student going into the nursing profession, I am particularly interested in the ever-growing number of nosocomial infections and what the health care industry is doing to try and reverse the incidence of such diseases. I’m also interested in science-fiction. When I saw this article, which combines remedy and robots, I had to jump on the opportunity to share this with everybody.

Come To The Dark Side

Hospitals have long been regarded as the shining light of healthcare to those who are injured or infirmed. Within these facilities, everything from the delivery of lives to the saving of lives is carried out on a daily basis. Yet today, more and more patients are entering hospitals and leaving sicker than they were when they entered. It important to identify why this is happening to patients and determine what the health care industry is doing to help prevent these avoidable illnesses. Let’s explore hospitals, “the dark side” of health care.

Rooms are cleaned, linens are sterilized, hands are washed, gloves are donned and masks are worn. Yet despite all of this, germs aren’t going anywhere. These resistant “superbugs” are responsible for making approximately 1 in every 20 patients in U.S. hospitals sick with nosocomial infections. These infections are coming at a high cost to not only the general public’s health, but also our wallets. According to the Centers for Disease Control and Prevention, these infections lead to an estimated 100,000 deaths every year and rack up a bill in upwards of $30 billion annually. As a result, insurers are striking back against hospitals. In fact, Medicare is proposing to stop paying for complications related to nosocomial infections. Clearly, the situation is grim.

 

Revenge of the C-Diff

Table 2, from Inweregbu et al, DOI 10.1093/bjaceaccp/mki006

So how did we get to this point? Was it: A) The Millennium Falcon, B) Podracer, C) Sandcrawler or D) The Sith? If you chose D) The Sith (better known in healthcare as “C-diff”) then you chose correctly!

According to Jennie Mayfield, the president-elect of the Association for Professionals in Infection Control and Epidemiology, the intestinal bug Clostridium difficile (C-diff) was the catalyst for stricter precautions with regards to infection control. The outbreaks from C-diff started about a decade ago, and today are responsible for around 14,000 deaths in the U.S. annually.

C-diff is just one example of an etiologic agent of nosocomial infections. Gram-positive bacteria are the most common cause of these infections, with Staphylococcus aureus being the most prevalent pathogen. The table shows the most common pathogens associated with nosocomial infections in ICU patients from January 1989-June 1998.

 

A New Hope

If C-diff and other resistant strains of bacteria represent the Sith within the dark side, then who or what will defend the good our nation? Well the Jedi order, of course!

“You can’t win, Darth. Strike me down, and I will become more powerful than you could possibly imagine.” – Obi wan Kenobi to Darth Vader in Star Wars, Episode IV: A New Hope

Germ-resistant copper bed rails, call buttons and IV poles are being made. Linens, curtains and paint are being made with antimicrobial substances. Machines resembling robots from Star Wars, which emit ultraviolet light and/or hydrogen peroxide vapors, are coming in to use good forces to rid hospitals of these evil superbugs.

Xenex Healthcare Services makes a portable machine that zaps these superbugs dead by using ultraviolet light. Xenex has sold (at $125,000 a piece) or leased devices to more than 100 hospitals throughout the U.S.  One hospital that is using this technology is Westchester Medical Center. During the last two years, a study showed that C-diff infection rates fell by half and C-diff deaths fell from 14 to 2; a dramatic decrease compared to the two years before the machines.

It seems as though these machines are able to able to destroy the menaces that hand sanitizers and bleach cannot, but some experts say there still isn’t enough evidence to prove their worth. Dr. Clifford McDonald of the Centers for Disease Control and Prevention pointed out that “It only takes a minute for a nurse or visitor with dirty hands to walk into a room, touch a vulnerable patient with germy hands, and undo the benefits of a recent space-age cleaning.”

Yes, environments will get dirty again, but in this day and age of bacteria that is becoming harder and harder to eradicate, we need every ally possible to help protect the health of our loved ones and ourselves. There is no one foolproof way to keep us safe from nosocomial infections, so a variety of methods must be employed. I, for one, would be happy to have R2D2 on my side. May the force be with you!

Good bacteria helps bad breath

Marissa Weinfeld (3 PM Micro) found this article about halitosis and the oral microbiota. Her advice? Add more bacteria. Long time readers of BIO230 may recall my take on this topic from March 2011 (sorry Marissa–All That Has Happened Before Will Happen Again.)

Most people occasionally have bad breath however; about 25 percent of people have chronic bad breath.  Researches have discovered that the gas emitting bacteria on the tongue and below the gum line are responsible for the bad breath but have had a difficult time determining how to get rid of these bacteria responsible for the odor. Solutions to bad breath including mouthwash, brushing and flossing after meals may cause temporary relief but can also cause unpleasant side effects. Evidence from recent research has found that it is more effective to nurture helpful bacteria in the mouth rather than destroying the offending germs and their by-products.

Hydrogen sulfide and methyl mercaptan are found in higher levels in breath of bad breath individuals. These as well as other compounds are waste products released by the bacteria eating particles of food and tissue in our mouth. Gram-negative bacteria that live below the gum line and on the tongue produce more of the bad odors in breath. Mel Rosenberg a microbiology professor at Tel Aviv University and his colleague Nir Sterer recently found that some strains of gram-positive bacteria secrete an enzyme that clips sugar molecules off the proteins found in food, which makes those proteins more digestible for nearby gram-negative organisms. When gram-negatives digest proteins the more odors are emitted.

Current treatments that are said to improve oral ecology are found to make problems worse. A chlorhexidinse rinse was found to temporarily change the taste of food and was also found to cause a tingling or burning sensation on the tongue after a week of use on some users. Another find was that rinses with alcohol could dry out the mouth adding to the odors causing bad breath. It can also wipe out too many of the mouths normal bacteria allowing opportunistic species responsible for gum disease and other infections.

A researcher Rosenberg, developed a two-phase oil-and-water rinse that temporarily reduces bad breath by soaking up some of the oral debris and microbes that tooth brushing, flossing and tongue scraping miss.  Other researchers found that Streptococcus salivarius K12 can fight bad breath. In a study volunteers gargled with chlorhexidine mouthwash and sucked on lozenges laced with K12. A week to two weeks later they had much better breath. At U.C.L.A. a researcher is working mouthwash that contains peptide, which is tailored to selectively kill S.mutans, the bacterium that causes tooth decay. Using this in moderation may help bad breath. Research continues to find the cure for bad breath but for now the best solution seems to be good bacteria.

Fear as an agent of good?

The graph shows the annual number of cases of various cancers worldwide. The fraction of cancers estimated to be induced by HPV is shown in red. For example, nearly all cases of cervical cancer are believed to be caused by HPV. Parkin, D. M. (2006) (Photo credit: Wikipedia)

Our recent discussion about viruses and cancer led Afolake Ogunfuwa (3 PM Micro) to find this summary about the Human Papilloma Virus vaccine:

The  Science daily news website published a discussion about a study carried out by researchers in Ohio State University on the Human Papilloma Virus (HPV) vaccine. The study seemed to suggest that researchers concluded that a promotion of HPV vaccine use, based on scaring the population about cancer may not be working. They maintained that emphasizing the fact that the vaccine prevents a Sexually transmitted disease (STD) may be the way to go.

The website suggested that there is a conventional wisdom that: getting women vaccinated by scarring them is the best way to get them vaccinated. They further mentioned that the “cancer-threat” message has failed and attributed that statement to a lead author of the study on the HPV vaccine, an assistant professor of communication by the name of Janice Krieger. Apparently, the study maintained that women don’t respond to cancer threat, and that young women seemed more worried about getting an STD.      The website discussion went on to briefly describe the study and the driving idea behind it. The conclusion of the study apparently was that putting emphasis on the HPV vaccine ability to prevent genital warts was a clear winner with young women.

New Way to Treat Bed Bugs

Bed Bugs!

Sandra Malinowski found this article regarding an insect vector, and the microbial flora they carry. Here is Sandra’s summary:

Many of us have said or heard “don’t let the bed bugs bite” before getting ready to go to sleep, I know my grandma always said that to me before bed.  What we don’t realize is that bed bugs are actually a real parasite.  These bed bugs are scientifically known as Climex lectularis and are small bloodsucking arthropods that can fit into any small cracks or crevices in our homes.  Most people don’t have issues with them throughout their lives but if they do they cause great grief trying to eliminate them.  They are most common in places where there are a lot of people and cleanliness is not the greatest, like dormitories, military barracks, and hotels, although they are not confined to just these places.  I remember seeing a television show where a camp was infested with bed bugs and they spend three years trying to get rid of them while almost going bankrupt because of them.  Bedbugs cause red itchy spots on its victims, which makes this hard to diagnose because they are similar to other insect bites and bed bugs are hard to see.

As it turns out an article on Science Daily discusses how Cincinnati has been experiencing real problems with bed bugs for several years.  They are one of the top bed-bug infested cities by pest control companies such as Terminex and Orkin, which has become a great trouble for them because bed bugs have posed increasing resistant to many insecticides.  The Cincinnati health department decided that they needed to organize a bed bug strategic plan to reduce the infestation wreaking havoc on the city.   Regina Baucom, and assistant professor of biological sciences at the University of Cincinnati decided to do something about these pests.  She started studying the DNA of local bed bug populations and found a way to better eliminate these resilient insects.  She saw the insect’s resistance to insecticides and pest control and realized that she needed to find an alternative way to eliminate these organisms.  In order to better understand these local bed bugs Baucom and her team performed a genetic analysis on 31 different bed bugs within 8 different residencies in Cincinnati which helped her to analyze other microbes present within the bed bug’s environment.

Baucom and her team discovered that there were two different bacterial types present in 97 percent of the microbial communities.  These included Wolbachia and an unnamed gamma proteobacteria.  The proteobacteria is not known much about but probably aids the bed bugs in growth somehow due to its presence.  More importantly the Wolbachia is a nutritional mutualist and helps the bed bugs with reproduction and growth.  By isolating these bacterium Baucom could then target these organisms in the pest control to greatly reduce the number of bed bugs due to the important role that they play in the health of a bed bug.  Since bed bugs are so hard to kill and pose a great nuisance for humans Baucom intuitively found a better way to decrease these organisms by not directly killing them but indirectly by eliminating factors that were aiding in their survival.  This was very helpful in the search for a better way to eliminate bed bugs, especially since they can pose a threat to a person’s psychological health and trigger allergic reactions.  Bedtime shouldn’t be a time to worry about creatures biting us, but a relief period.  Think of that next time someone tells you “not to let the bed bugs bite”, because it’s a real threat.