Are We Creating Our Own Superbugs?

When you go into the doctor’s office complaining of a sore throat, you are probably thinking that the doctor is going to give an antibiotic to beat that little bug.  In fact, many people will go to their doctor asking for a Z-Pak or something like it.   Many doctors will comply and give you an antibiotic without even really thinking about it.  If this is what happens at your doctor, research has shown there’s a high likelihood that both you and your physician are treating your sore throat incorrectly. 

 

            In general, antibiotics are used to treat bacterial infections but they do not have an effect on infections caused by viruses.  Among those who visit a doctor complaining of a sore throat, only about 10% will have an infection that is caused by a bacteria and can be treated with an antibiotic.  The bacteria causing a sore throat that can be treated by antibiotics is called group A Streptococcus.   Of the sore throat infections susceptible to antibiotics, penicillin is the recommended treatment.  

 

Group A Streptococcus Bacteria—Only 10% of total sore throat cases

http://www.gov.mb.ca/health/publichealth/diseases/gas.html

 

Researchers from Harvard University decided to take a look into just how often antibiotics were being unnecessarily prescribed to patients with sore throats.  They went through data collected from 1997 to 2010 in order to see any trends in antibiotic prescription; whether it was increasing or decreasing over time.  The researchers got their data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Care Survey which are both yearly surveys that collect data nationwide regarding treatments, diagnoses, and the patient’s reason for visiting.  During the study, 8191 sore throat visits were sampled.  From a survey that was done from 1989 to 1999, we know that the rate of antibiotic prescription for sore throats was at a high of around 80% in the early 90’s.  The most recent study showed that this number has been steadily decreasing since then and was around 60% in 2010. 

It was also found that from 1997-2010, the prescription of more expensive, broad-spectrum antibiotics (those that are not penicillin) was very common, and was on an increasing trend.  Azithromycin (Z-Pak) prescription increased to about 15% of all sore throat prescriptions in 2010.  Penicillin prescription however remained constant and comparatively infrequent during the time period of the study. 

 

Efforts to educate the public and healthcare providers about the frequency and effects of prescribing unnecessary medications have been a major factor in this continual decrease.  The Center for Disease Control has mainly lead campaigns aiming to reduce unnecessary antibiotic use.  This may all seem like good news that the proportion is decreasing, but considering that only 10% of sore throat cases should result in the prescription of an antibiotic, 60% is still way too high. 

 

You may now be wondering why this is such a big deal.  Why does it matter that some patients take antibiotics even if they don’t have to?  Besides the general concern that comes along with putting unnecessary compounds in your body that may cause allergic reactions and other side effects such as diarrhea, inappropriate prescription of antibiotics can lead to superbugs.  When an infection is treated with antibiotics, but the medication doesn’t get rid of it entirely the result can be the development of strains of the bacteria or virus that are not resistant to those antibiotics.  These strains are often called ‘superbugs’ because they can’t be cured with standard medications.  Superbugs pose a very serious health threat because if it becomes a particularly aggressive strain, it can infect many people when we have no way of stopping it. 

            Even besides health repercussions, over prescribing of antibiotics can cost the country large avoidable sums.  The broad-spectrum antibiotics such as azithromycin that are becoming more common can be up for 40 times more expensive than the recommended penicillin prescription.   It was estimated in the study that from 1997 to 2010 the nation spent about $500 million on antibiotics for sore throat patients that didn’t need them. 

           

            Based on the study, there is still work that needs to be done to educate both patients and doctors on proper antibiotic usage and the possible effects of over-prescribing unnecessary medications. 

 

Sources:

http://www.sciencedaily.com/releases/2013/10/131004105256.htm

http://archinte.jamanetwork.com/article.aspx?articleid=1745694#ild130146r2

Middle East Respiratory Coronavirus – The Next Deadly Epidemic?

A recently discovered virus could be the next deadly epidemic in humans. Middle East Respiratory Coronavirus, or MERS-CoV for short, was isolated from a patient in Saudi Arabia in March of 2012 and has since been implicated in deaths across the region. While the virus has been a hot topic of research over the past year, with at least 63 papers published, epidemiologists have only recently characterized the possible extent of human transmission and mortality. In a paper published in Lancet on November 13, researchers attempted to give a comprehensive look at how virulent the disease may be.

 

What is a coronavirus?

The Center for Disease Control states that coronaviruses are one of the most common types of virus worldwide and that most people will be infected by one at some point in their life. They can be transmitted from human to human or between animals and humans and are usually more irritating than deadly. This is certainly not always the case however; in those who are immunologically compromised, coronaviruses can cause symptoms as severe as pneumonia. The most well-known example of a coronavirus is SARS, which caused over 700 deaths at the beginning of the 21^st century. Several papers have drawn comparisons between MERS-CoV and SARS, and many fear that the new pathogen could cause a deadly outbreak if public health measures are not utilized appropriately.

Photo courtesy of: http://www.neatorama.com/2013/05/29/Meet-The-Latest-Thing-That-Can-Kill-Humanity-MERS-CoV/

 What we know about MERS-CoV

 Despite being the focus of a relatively high number of papers, our knowledge of MERS-CoV is somewhat limited. The exact method of transmission of the virus has not been determined, although camels and bats are both believed to be reservoirs. The majority of cases have been confined to the Middle East, and especially Saudi Arabia, however infections in the UK, France, and Tunisia have been linked back to travel in the region. Although discovered fairly recently, MERS-CoV has been implicated in at least 111 cases as of August 2013. Of these 111 cases, 46 were fatal. While the high number of fatalities is shocking, researchers estimate that there have likely been at least 940 cases, the majority of which have gone unreported.

 

The study in Lancet sought to compile a comprehensive database of all the reported cases thus far in order to learn more about the virulence of the virus. The authors found that the virus is significantly more deadly in patients over 50, with 77% of cases ending in fatality compared to 22% for those under 50. They looked at animal-human and human-human transmission models and determined that visitors to the Middle East were at a higher risk of transmission from reservoir animals than locals. The most significant finding from the database was that the value of R for MERS-CoV was slightly above 1 but could be decreasing. This means that transmission is not 1-1 and therefore self-sustaining, but it is close. Given how incomplete the current data on MER-CoV is, the researchers estimate that R may have already dropped below 1. More cases must be observed before it can be conclusively determined how quickly the virus spreads, however it is likely already at epidemic status.

 

Photo courtesy of: http://www.sott.net/article/262615-Middle-East-Respiratory-Syndrome-Coronavirus-MERS-CoV

What this means for us

Although MERS-CoV is deadly, few cases have been reported outside of the Middle East and none of them have occurred in the United States. If researchers are correct that the majority of cases have gone unreported, it is also likely that many of these cases are mild and do not lead to death or even hospitalization. Furthermore, a pharmaceutical company recently announced that they had begun clinical testing of a vaccine to the virus. If the vaccine is successful and combined with a robust public health program, it is possible that MER-CoV could be contained before it spreads much further. Ultimately though, it is necessary for research to continue and for the public to be aware of the virus as tourists to the Middle East could potentially spread the disease across the world.

Sources:

The study in Lancet – thelancet.com/pdfs/journals/laninf/PIIS1473309913703049.pdf?id=8b69abadd6dadf97:4d51d508:14292206b53:-6e951385431584619

 CDC Information on coronaviruses – http://www.cdc.gov/coronavirus/about/index.html

Information on a MERS-CoV vaccine – http://www.theglobaldispatch.com/inovios-mers-vaccine-syncon-dna-vaccine-induces-robust-and-durable-immune-responses-in-pre-clinical-testing-84427/

New Avian Flu Virus emerges in Taiwan: Researchers show that a commonly used food preservative was able to prevent H7N9 from entering the cell of the host

What is Avian Influenza H7N9 virus ? 

 H7N9  is a recently found bird flu strain of the species of Influenza Virus A. There are many different subtypes of A influenza viruses. These subtypes differ on differences in two main proteins on the surface of the influenza A virus , they are  Hemagglutinin HA and neuraminidase NA proteins. There are 16 known HA subtypes and 9 known NA subtypes of Influenza A viruses. Avian influenza A H7 viruses normally circulate amongst avian population with some variants known to infect humans. H7N9 has recently been reported among domestic chickens with few cases of human infections in Taiwan.

Researchers have found that using a commonly used food preservative can prevent H7N9 from entering the cell of the host. This food preservative is tert-butyl Hydroquinone ( TBHQ), is a highly effective antioxidant. This could be a simple and effective way of keeping the viral load down in the host and preventing the virus from spilling over into human

 

 Photo courtesy of http://www.Bloomberg.com

 

How does tert-butyl Hydroquinone( TBHQ) works?

In foods, it is used as a preservative for unsaturated vegetable oils, and many edible animal fats. It has been proven that H7 hemagglutinin ( HA) plays an important role in influenza entry and therefore HA presents an attractive target for antivirals.  In a recent study done by Michael Caffrey, associate professor of biochemistry and molecular genetics at the University of Illinois at Chicago, shows that  TBHQ inhibits the entry of influenza H3HA by stabilizing the neutral pH conformation of HA, thus disrupting the membrane fusion step of the virus. Such finding is critically important since, by removing proteins on the virus surface involved in recognizing, binding to and entering the host cells, the virus itself can be stopped from spreading or causing harm to the host.

In his study Dr. Caffrey collected H7N9 samples and tested the success of the inhibition of the food preservative TBHQ in a lab setting. He noted that HA, as well as the analogous envelope proteins from Ebola, HIV, and SARS-CoV, mediates virus entry through receptor binding and conformational changes that result in fusion of the viral and target cell membranes. He concluded, that the H7N9 binding region is an attractive target of therapeutic intervention and that TBHQ is a promising leading compound. 

Why do we care?

 Inhibition of Influenza H7 hemagglutinin, presents vast opportunities for treating influenza. One of those possible methods of treatment is tert-butyl Hydroquinone (TBHQ ) a food preservative which may present the potential for addition to animal feeds, including those for bird, the transmission agent of H7N9 influenza as an antiviral agent.  

 It is very important to be able to treat, and contain the pathogen to its host, and prevent it from spilling over into humans.  This is especially important since the pathogen at hand affects birds that are consumed by humans and or in one way or another in contact with them. A spillover is an event in which a pathogen from one species moves into another species, such movement can result in an outbreak. There have been in the past outbreaks of different strains of the Avian flu that have effected entire populations around the world. It is why it is critical to contain and treat H7N9 in birds, to avoid the next human pandemic. 

 

 

 

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0076363

http://www.uic.edu/com/bcmg/faculty/caffrey_michael.html

 http://www.bloomberg.com/news/2013-04-08/chinese-asked-to-change-eating-habits-as-h7n9-infections-rise.html

 

The Role of MCPIP1 in HIV Infection

HIV Background

The World Health Organization estimates that globally 35.3 million people are infected with Human Immunodeficiency Virus (HIV).  Many of these infected people live in Africa and Southern Asia.  This virus is transmitted between humans through bodily fluids including semen, blood, breast milk, and vaginal fluid.  HIV infects CD4⁺ T cells.  CD4⁺ T cells are part of the immune system and play an important role in protecting humans against infections.  This infection of CD4⁺ T cells often leads to cell death.  People who have CD4⁺ T cell counts below 200 cells/mm³ are classified as having Acquired Immunodeficiency Deficiency Syndrome (AIDS).  AIDS patients are highly susceptible to opportunistic infections especially tuberculosis and may die from these infections.  Since 1981, AIDS has been responsible for the deaths of over 25 million people globally.  Currently, highly active anti-retroviral therapy (HAART) is used to treat HIV-infected patients.  HAART prevents the replication of HIV and reduces the level of the virus in the patient’s body.  This decreases the chances of the patient progressing to AIDS, yet HAART does not completely eliminate HIV.  Currently, there is no cure for HIV.

HIV Structure

HIV is a retrovirus in the lentivirus subfamily.  The genetic material of HIV is composed of 2 strands of mRNA.  These RNA strands are surrounded by a protein capsid shell, and this capsid shell is surrounded by a lipid envelope.  There are several enzymes located in the capsid shell which are necessary for HIV replication including integrase, reverse transcriptase, and protease.  The lipid envelope contains transmembrane glycoproteins which can bind cellular receptors.

http://micro.magnet.fsu.edu/cells/viruses/hivvirus.html

HIV Replication

To infect a CD4⁺ T cell, the HIV glycoproteins first bind to the CD4 and CCR5 cellular receptors.  This causes the lipid envelope of HIV to fuse with the cellular envelope, and the viral core is released into the cellular cytoplasm.  Then the RNA genome of HIV is reversed transcribed into DNA, and this DNA is integrated into the cell’s genome.  This integrated DNA may be used to make more copies of HIV.  This occurs when the DNA is transcribed into the virus’s RNA genome and translated into viral proteins.  The new virus then assembles in the cytoplasm and buds from the cell.

http://www.southsudanmedicaljournal.com/archive/2009-08/untitled-resource.html

Resting vs. Activated CD4⁺ T cells

CD4⁺ T cells exist in either a resting or activated state.  A major difference between these two states is that activated CD4+ T cells are dividing, while resting CD4⁺ T cells are not.  Activated CD4⁺ T cells are the primary target of HIV infection.  When activated CD4⁺ T cells are infected, HIV replicates and more virus copies are produced.  HIV is also capable of infecting resting CD4⁺ T cells, but this infection does not often lead to viral replication.  A recent paper published in the Proceedings of the National Academy of Sciences by Shufeng Liu and colleagues provides insight into the mechanism responsible for this difference.

MCPIP1 and HIV Infection

Monocyte chemotactic protein-induced protein 1 (MCPIP1) is involved in the regulation of the immune system.  When Shufeng Liu and colleagues expressed MCPIP1 in HIV-infected T cells, HIV production was inhibited.  The amount of HIV DNA in the genomes of the cells remained the same in the presence of MCPIP1.  However, the level of HIV RNA in the cells was significantly lower.  Previous studies found that MCPIP1 has RNase activity (can degrade RNA); therefore, MCPIP1 may be blocking HIV replication at the transcription stage.  To test this hypothesis, HIV replication was measured in the presence of mutated MCPIP1 that no longer had RNase activity.  The level of HIV replication in the cells with mutated MCPIP1 was similar to the replication level when MCPIP1 was absent.  The scientists then wanted to test the expression level of MCPIP1 in activated CD4⁺ T cells.  The CD4⁺ T cells were activated using mitogens that cause cell replication.  MCPIP1 levels were significantly lower in activated CD4⁺ T cells leading to the conclusion that MCPIP1 had been degraded by these cells.  Overall, this study found that MCPIP1 decreased HIV replication in T cells and that activated CD4⁺ T cells degraded MCPIP1.  Thus, MCPIP1 may be partially responsible the decreased level of HIV replication in resting CD4⁺ T cells as compared to activated CD4+ T cells.

Reference: http://www.pnas.org/content/110/47/19083.full.pdf+html

Using Fish Interferons to Study Human Antiviral Defense

What is an interferon?

Interferons (IFNs) are part of a key antiviral defense system in vertebrates. In essence, IFNs are proteins made and released by cells in the response to the presence of viruses, bacteria, parasites, or tumor cells. No matter what illness you get from the guy at work, or the kids at school, or the old lady on the bus, IFNs are circulating around your body trying to keep you healthy. In humans, IFNs come in three different flavors, or types: cleverly named type I, II, and III. Each type of IFN plays a slightly different role in the cell, but all share the common goal of eliminating viral agents and providing defense against tumors. Usually, its anti-viral properties are the result of downstream signaling, usually with help from another type of protein, STAT complexes. STAT, along with its associated protein, JAK, promote other proteins that cause DNA transcription of proteins to help combat pathogens.

The latest on interferons

For the first time in vertebrates, scientists have demonstrated that alternative splicing of IFN genes can lead to a functional intracellular IFN (iIFN). Put simply, after RNA copies a message from DNA, the RNA can be cut in a variety of different ways that produce different proteins. In this case, the IFN genes are cut in such a way that the cell will hold on to the IFN instead of releasing it. Usually, IFNs are secreted by a cell and need to interact with receptors on another cell’s surface in order to function. Therefore, instead of cells releasing the anti-defense proteins, it will simply hold on to them and defend a pathogen from within. Then, the iIFNs will elicit cellular responses through intracellular IFN receptors.

Using fish to study IFNs

Multiple genes are used in the formation of IFN proteins. For instance, in humans, the genes are found on chromosome 9 and chromosome 19. In addition, humans mainly use type I and III IFN families. In order to study IFN interactions, scientists often use bony fishes as a convenient way to study the interactions between IFNs and other proteins. The type I IFN family consists of proteins that are encoded by intronless genes in reptiles, birds, and mammals, but intron-containing genes in amphibians. Fish IFN genes possess the ability to stay within the cell because they are missing a signal peptide. Signal peptides are little peptide sequences attached to a newly synthesized protein that directs the protein where to go. Just pretend that signal peptides are like a GPS in a car – a small device that points you in the right direction. This presents a problem when studying IFNs in fish because the findings related to fish might not necessarily be applicable to humans.

Using rainbow trout is an effective way for scientists to study IFNs.

Image courtesty of http://www.deneki.com/

How does this help us?

In a study by Ming-Xian Chang and his collaborators across the world, they used rainbow trout to demonstrate the above process. Based on this study, it is reasonable to think that the iIFNs in the trout they studied would be able to quickly trigger an antiviral response immediately following a virus infection. This is important because viruses are constantly finding ways to disrupt the normal IFN pathways in order to flourish inside the trout, or to hit home, human bodies. In addition, Chang postulates that all of the extra iIFNs that a cell makes could be stored inside the cell and released all at once during a viral infection. This would essentially initiate an alarm system within the body – neighboring cells would be alerted and they too would release IFNs to combat the infection.

Great – so let’s just load up on iIFNs…

Not so fast. This novel defense to combat viral pathogens is at the early stages of investigation. This type of antiviral defense will take years, if not decades to fully perfect before it can be used in a clinical setting. However, this study provides an excellent starting point for future study of iIFNs as use as a novel defense against pathogens.

To read more, click here.

Chlamydia Vaccine? Go Away STD!!!

Sexually transmitted diseases (STDs) are extremely prevalent in our society today. They are easily transmitted, and take some time before showing symptoms while some do not show any. According to the US Centers for Disease Control (CDC), among STDs Chlamydia trachomatis is the most common reported disease in 2011.

The scary part about Chlamydia infections is that a lot of the time they are asymptomatic. Therefore, the disease is being spread frequently without the hosts even knowing. Continuous infection of Chlamydia can lead to chronic pelvic inflammation or doom some women infertile.

The rapidly growing prevalence of Chlamydia in combination with its undesirable consequences emphasizes the importance of creating a vaccine to lower the transmission rates and the overall infection.

However, it is difficult to create a vaccine because as of now there is not much known about how the immune system responds to the infection inside the female reproductive tract. In this study, two brilliant researchers Lin-Xi Li, and Stephen J. McSorley discovered that cells specific to working against Chlamydia (set of CD4 T cells) are triggered by the presence of another type of cell (B cells), which aid the immune system in fighting off the bacterial infection.

Why do we care? Well, knowing how the host immune system functions in response to Chlamydia will help the development of a vaccine so that another STD can be further controlled.  

To begin understanding how the host immune system works, researchers experimented on mice. Their first task was to test their hypothesis that specific CD4 T cells are made when the host is infected, which causes a delay in the response in the genital tract compared to the response of a systemic infection. To test if a delay ever happens, the researchers infect mice with Chlamydia muridarum and then measure the presence of specific CD4 T cells. They observed a peak in specific CD4 T cells after 14 days in response to the induced bacterium, which confirmed that the response by the genital tract was delayed.

Next, they wanted to learn more about the helper response, which basically brings more help to fight off the infection. The immune system is comprised of different responses depending on what type of help is needed. They found that Th1 response dominates, which basically tells other cells (B cells) to come along and help out.

To look more into the role that B cells have on the immune system during Chlamydia infection, the researchers examined mice without B cells. They collected accumulating fluid from the mice lacking B cells, which contained cells specific to the infection. Therefore, they noted that the presence of B cells is necessary for priming the T cells to initiate a more specific response.

So in summary what does all this tell us? Well, the researchers were able to show that there was a difference in time from when the CD4 T cells showed up depending on if the infection was systemic or in the genital tract. Since the female genital mucosa lacks lymphoid structures, they believe this may be one reason for the delayed response of clonal expansion of T cells. Also, they used a specific epitope when recognizing the induced bacteria infection in their research. It is basically the key and the bacterium is the lock. Their success with this “key” is consistent with other studies that show potential use of this epitope for vaccines.  To further understand the host response, they found out that Th1 response is dominant after infection, which aids the cells in killing off the bacteria by calling B cells to help. They found that when B cells are not present, the bacteria tends to take over and can lead to accumulation of fluid in the peritoneal cavity.

All of this information is important because the human immune system is so complex, and knowing these little details gets us a lot closer to making the perfect vaccine. Chlamydia is easily and widely spread across the country, and it is important that we find ways to control this infection with a vaccine before all become infected!

 The link for the paper can be found here.

Article Citation:

Li L-X, McSorley SJ (2013) B Cells Enhance Antigen-Specific CD4 T Cell Priming and Prevent Bacteria Dissemination following Chlamydia muridarum Genital Tract Infection. PLoS Pathog 9(10): e1003707. doi:10.1371/journal.ppat.1003707

Dengue Fever in Houston

Houston, we have a problem. And it is a potentially fatal problem. A recent study, led by Dr. Kristy Murray of the Baylor College of Medicine, has showed that the tropical viral disease dengue fever has been dwelling in Houston for the past decade.

What is dengue fever?

Dengue fever is a very serious tropical disease caused by one of four dengue viruses. It is spread to humans by mosquitoes of the Aedes genus, primarily Aedes aegypti. It has no known cure or vaccine.

The Center for Disease Control states that dengue is a leading cause of illness in tropical regions, with up to 100 million infections and over 22,000 deaths annually. Since its dramatic rise in the 1960s, dengue is now endemic in over 110 countries. Over one third of the global population live in areas at risk for dengue, including northern South America, Central America, Mexico, central Africa, India, south Asia, all the island nations in southeast Asia, and small regions in northern Australia.

Dengue is rarely seen in the United States. The disease was thought to be eradicated from the continental US in the 1990s. However, in the past decade, there have been reports of dengue along the Mexican border, Hawaii, and southern Florida.

About twenty percent of infected individuals display no symptoms. The other eighty percent of patients may experience high fever, joint pain, muscle pain, headache, vomiting and a distinctive skin rash. In less than five percent of cases, dengue hemorrhagic fever can occur. In addition to typical dengue symptoms, the capillaries (tiny blood vessels) become leaky and easily bleed. In the most severe cases, bleeding can lead to circulatory system failure, dengue shock syndrome, and death.

According to Dr. Peter Hotez, dean of Baylor’s National School of Tropical Medicine, there are several strains of the dengue virus. Bad news occurs when a person who recovers from one type of dengue fever becomes infected with another type. Dr. Hotez states that having antibodies against one type somehow has synergy with the other type, leading to a much higher chance of dengue hemorrhagic fever.

How did they find dengue in Houston?

Surveillance for dengue fever in the US is lax, even though places like Houston are environmentally conducive for the virus. Therefore, Dr. Murray’s team decided to search for signs of dengue in samples of serum and cerebrospinal fluid in patients. These samples were collected between 2003 and 2005 from patients with suspected mosquito-borne viral infections, primarily West Nile Virus.

The researchers looked for a certain immunoglobulin, or antibody, in the samples. Its presence would indicate that the patient was exposed to dengue. From the 3,768 samples, the researchers discovered 47 cases of dengue. Two of the cases were fatal; one of the two displayed symptoms consistent with dengue hemorrhagic fever. While this number may not seem very impressive, keep in mind that the samples were only obtained from the most ill patients.

The researchers pondered the possibility that the virus was brought back by patients visiting tropical locales. However, they found that the majority of positive samples came from patients who had never left the city. Dr. Murray thinks that it is pretty clear there was an outbreak in Houston during that time period.

What now?

Dr. Hotez  stresses the need for “aggressive surveillance”. He states that monitoring dengue is critical not only in Houston but also across the Gulf. Dengue has existed in Key West, Florida since 2010, and has been spreading since earlier this year. Dr. Hotez says that if either the Houston or Florida strains spread across the Gulf Coast, the increase in dengue hemorrhagic fever would result in a fatal outbreak.

Dr. Murray reiterates the need for alertness. She states that our currently passive surveillance and diagnostic measures must be improved upon. Because dengue has no cure or vaccine, vigilance is the best we can currently do to preempt a major problem. So for now, just be sure to pack plenty of bug spray.

 

Original Article

http://online.liebertpub.com/doi/full/10.1089/vbz.2013.1413

Other Sources

http://www.npr.org/blogs/health/2013/10/16/235628882/houston-we-have-dengue-fever

http://www.chron.com/news/health/article/Dengue-virus-identified-in-Houston-4883103.php

http://www.cdc.gov/dengue/

Unexpected Side Effects – Contaminated Steroid Injections Cause Meningitis and Other Infections

http://www.spine-health.com/images/syringe.jpg

Although America has one of the top health care systems in the world, it isn’t always perfect. Recently there has been an investigation of one of the largest documented healthcare-associated outbreaks in which fungal meningitis and other infections affected patients that had received epidural, paraspinal, or joint injections with a contaminated form of methylprednisolone acetate, which is a steroid often used for patients suffering from pain and swelling secondary to arthritis and other joint disorders. Since infections are usually not common in these injections which are commonly used for treatment, the investigation found that these secondary infections were being caused by a rare human pathogen known as Exserohilum rostratum.

 

http://www.cdc.gov/fungal/other/exserohilum-rostratum.html

 

What is Exserohilum rostratum?

Exserohilum rostratum is typically considered to be rarely found in humans, and it is a common type of mold that is found in soil and on plants. Usually when it does happen to infect a human, there it has been known to cause a different variety of infections ranging from skin infections to more invasive ones such as infections of the lining of heart and of the lungs.

 

How did these patients get infected?

The investigation found that patients were getting infections from steroid injections of contaminated methylprednisolone acetate that yielded from a particular pharmaceutical company.  Although the exact means of how the fungi affected the central nervous system, it is believed that the injection of the contaminated drug would have been the most plausible since the patients presented with infections near the injection site. The symptoms of these patients varied and the severity of their secondary infections ranged from mild to life-threatening.

For this the investigation the researchers categorized the main disease types that afflicted most of the patients presenting with the infection. The most common disease type that was found during this outbreak was meningitis, although there were a variety of other diseases that arose from infection including but not limited to stroke, arachnoiditis and intradural abscess. The investigators divided the patients into two broader categories that separated them between being affected by central nervous system diseases (such as meningitis and stroke) and non-central nervous system diseases (such as joint infection).

 

Types of Disease Found and Implications

As previously mentioned, the investigation divided the diseases arising from implications as either CNS (central nervous system) diseases or non-CNS diseases. Unfortunately, CNS diseases were more common in this investigation due to the nature of the injection, yet because of the nature of the types of injections that caused each, the investigators were able to retrieve information about the drug lot and vial age, tracing the drug back to the pharmacy that distributed the contaminated drug.

 

Conclusions of the Investigation and Take Home Points

The investigation sought to understand the cause of infections that were arising in patients that had received a particular type of steroidal injection most commonly used in treating arthritis and other joint problems. What was found was the contamination of the drug by a mold that is commonly found in soil and on plants and is known as Exserohilum Rostratum.

Although the study was able to further identify the cause of the infections in these patients, it was unable to fully explain the variety of the diseases amongst the patients. Some explanations included the site or type of injection, and others included health of patient prior to being injected with the contaminated drug. However, an implication that was brought to attention was the reporting of the infections at different times, and the limit of time in the study, in which the researchers were unable to fully investigate the course of the diseases over a period of time and were therefore unable to understand the incubation period of the fungi.

Although unexpected and unfortunate, the fungal outbreak allowed for the  increase in awareness of fungal infections and their effects, increasing literature on fungal infections and contributing to the understanding and betterment of diagnosis and treatment of CNS and paraspinal fungal infections.

 

Original Article:

http://www.nejm.org/doi/full/10.1056/NEJMoa1304879#t=article

 

Other Sources:

http://www.cdc.gov/fungal/other/exserohilum.html

http://www.webmd.com/drugs/drug-4454-Methylprednisolone+Acetate+Inj.aspx?drugid=4454&drugname=Methylprednisolone+Acetate+Inj

http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html

Is Pain Beauty? The danger of an opportunistic bacteria found in a case of cosmetic surgery.

http://dhindia.com/blog/wp-content/uploads/2013/02/cosmetic-surgery.jpg

There are many complications that can occur during and after cosmetic surgery.  Not only is it mentally, emotionally, and psychologically taxing, but it also puts increased stress on the body as it recovers and repairs itself after the surgery.  This weakens the immune system, and it is during this time of physiological recovery that infections caused by opportunistic bacteria may arise.

Recently, a case was reported of a middle aged woman with a history of facial cosmetic surgery (such as laser procedures and filler injections) was experiencing persisting edema, swelling, and tenderness on the right cheek.  Even after being prescribed an antibiotic, the patient’s condition did not improve.  After pus was collected from the infected area, cultured, processed, and tested, the bacterium responsible was found: Mycobacterium wolinskyi.

http://www.biomedcentral.com/1471-2334/13/479/figure/F4

What exactly is Mycobacterium wolinskyi?

Mycobacterium wolinskyi is one of the hundreds of species of mycobacterium that is not associated with tuberculosis (Mycobacterium tuberculosis).  These nontuberculous mycobacteria (NTM) are widely found in soil and water and rarely cause disease unless an aspect of the host is impaired.  NTM are further categorized into two groups – rapidly growing mycobacteria (RGM) and slowly growing mycobacteria (SGM).  Mycobacteria can also be classified using Runyon’s classification which divides them into four groups based on growth rates and pigmentational properties.  M. wolinskyi, a RGM, was first identified in 1999 and belongs to the Mycobacterium smegmatis group which is a type IV mycobacteria.  This means that M. wolinskyi grow rapidly but do not produce pigment.

What’s known about it?

Though M. wolinskyi is not commonly found in the clinical setting, it is mainly associated with skin and soft tissue infections (SSTIs).  Previously reported cases of M. wolinskyi involve incidences following surgical procedures such as hip prosthesis, peritoneal dialysis, and posttraumatic events.  Because this bacterium is opportunistic, immunocompromised patients are also much more vulnerable to infection by M. wolinskyi.  For instance, there have even been reports of bacteremia caused by M. wolinskyi in a patient that was diagnosed with lymphoma.  The immunosuppression caused by the treatment with the antibody rituximab and a steroid during chemotherapy may have weakened the patient’s immunity and thus allowed M. wolinskyi to cause infection.

What was so special about this case?

This case of M. wolinskyi was special because it was the first documented case of infection complicating facial cosmetic procedures.  One possible reason of infection may be due to contamination during surgical procedures and the failure of aseptic surgical technique.  Also, the patient had a history of receiving facial acupuncture as a child which could have left remnants of needles that would allow M. wolinskyi to invade the skin and proliferate along the existing metal fragments.

The usual route of bacterial infection is “acute exacerbation” and then the patient can recover by using antibiotics.  However, in some cases of chronic infection (as in this case with the cosmetic surgery patient) where there is antibiotic resistance, considering the possibility of NTM infection could help with quicker diagnosis and treatment which would then lead to a speedier recovery.

Why does this matter?

This one case emphasizes the possible risks and side effects of cosmetic surgery, but the implications can be generalized to other areas as well.  When the body is under increased stress and decreased fitness this can then create the perfect environment for opportunistic bacteria to strike.  Another example of this process occurs with the bacteria Clostridium difficile.  Normally C. difficile is in a non-active form and is kept in check by the other beneficial bacteria in the colon.  However, when antibiotics disrupt the growth of the beneficial bacteria, this activates C. difficile into its infectious form which causes physical symptoms and maladies.  

This case gives further emphasis on the characteristics of opportunistic bacteria and the emergence and increased prevalence of these strains.  As such, it shows the importance of being aware of opportunistic bacterial infection when the immune system is weakened or compromised by another disease.

References

http://www.biomedcentral.com/1471-2334/13/479

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2630732/

http://synapse.koreamed.org/DOIx.php?id=10.3947%2Fic.2013.45.1.85

http://water.epa.gov/action/advisories/drinking/upload/2009_02_03_criteria_humanhealth_microbial_mycobacteriaha.pdf

http://www.medilexicon.com/medicaldictionary.php?t=58137

 

Proposed HIV Vaccine Proved Ineffective

For years, scientists have been striving to better understand HIV and AIDS in hopes to treat and prevent this killer disease. However, despite the number of proposed vaccines, one has yet to consistently show decrease in transmission. This post will discuss Hammer et. al’s trial of one such proposed vaccine that has claimed success in Thailand by preventing the spread of HIV-1.

HIV-1 Background

Human Immunodeficiency Virus or HIV is the virus that causes AIDS (Acquired Immune Deficiency Syndrome) that already plagues 34 million people in just about every country around the world (who.int). And each year the number of people with HIV increases by 2.5 million. The most common strain of this virus is the HIV-1 strain which is now in its fourth decade. As we struggle to contain and eliminate this virus, we have yet to find an effective procedure of doing so. Currently methods such as treatment as prevention, are used, but not to much success. Therefore it stands to reason that the only way to control the spread of HIV is to find a vaccine.

VCR’s Proposed Vaccine

Although many vaccines have been proposed, only one has been able to claim any sort of success. This vaccine was developed and distributed by The Dale and Betty Bumpers Vaccine Research Center (VCR) of the National Institute of Allergy and Infectious Diseases and tested in Thailand among the general population. VCR’s vaccine aims to elicit a response in the T-cells and antibodies. T-cells are a type of white blood cells that fight off diseases, and are lacking in HIV/AIDS infected patients (tcells.org). In the VCR trials a 31% decrease in HIV infections were reported.  This study is a trial of this vaccine performed in the United States.

http://healthimpactnews.com/wp-content/uploads/2012/12/Vaccination_needle.jpg

How it Was Done

This trial was conducted from June 11, 2009 to March 27, 2013 (although the duration of the study for each participant only lasted for two years) using male and transgender women participants between the ages of 18 and 50. Each participant had to have had a history of unprotected `male with male intercourse (this included male to female transgenders) or male with male intercourse with at least two partners in the last six months. Furthermore, each participant underwent testing such as being tested for HIV-1 and HIV-2 antibodies. To partake in the study the participants had to test negatively for the antibodies.

Approximately 2500 participants partook in study, where they were randomly assigned into two groups, one of which would receive the vaccine and the other that would receive a placebo. The vaccine and placebo injections were administered at zero weeks (the start date of the study), four, and eight weeks with a booster administered at 24 weeks. Furthermore, patients were also given risk-reduction counseling which informed and gave participants the tools to reduce the risk for HIV/AIDS and other sexually transmitted diseases.

What They Found

Once the entire study had been completed, researchers had diagnosed 41 people who had received the vaccine and 31 people in the placebo group with HIV. Furthermore, researchers continued to screen participants for some time after their individual 24 month study had ended (until August 23, 2013), and found the number of people to have obtained HIV to have increased to 37 infected in the placebo group and 43 infected in the vaccine group. This closing of the gap as well as the limited behavioral risk difference between the two groups dismissed any notion that the vaccine may increase susceptibility to HIV.

What This Means

              So in conclusion, Hammer et. al.’s trial of VCR’s HIV-1 vaccine proves that the vaccine is not effective as was claimed by VCR originally. However, it is possible that potential other factors should be analyzed when drawing conclusions from this trial. Yes, those injected with the vaccine were infected about as much as those with the placebo, but were those rates lower than the rates of the tested population in Thailand? How does our education, health system and resources affect our infection rate in the United States compared to those in Thailand or in other countries? Meaning, while other measures may be used to reduce transmission rates, scientists must continue to search for a vaccine or some other method to control, and hopefully eliminate, the spread of HIV.

Article:

http://www.nejm.org/doi/full/10.1056/NEJMoa1310566#t=article

Additional Sources:

http://www.who.int/gho/hiv/epidemic_status/cases_all/en/

http://www.tcells.org/beginners/tcells/

Photo:

http://healthimpactnews.com/wp-content/uploads/2012/12/Vaccination_needle.jpg