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Influenza 101: This year’s flu and the next big concern

25th Sep 2015 Diseases, Viruses

It has been widely reported that this year’s flu vaccine is very ineffective. In fact, the CDC has now reported the vaccine effectiveness to be a dismal 18%. The reason for this is that the main virus that has been circulating, H3N2, is not included in this year’s vaccine. A universal vaccine is currently in clinical trials, but its effectiveness and release are currently unknown.

In review, there are three types of influenza or “flu” that affect humans (Type A, B, C). As we all know, the flu can cause symptoms that range from mild to severe including fever, sore throat, muscle pains, coughing, headaches, nausea, vomiting and lethargy. Type A influenza has been known to be associated with the worst outbreaks and cause the most severe disease. Wild birds are the natural host for this type of flu. While similar to the influenza virus, the avian form of influenza is from a different subspecies. All influenza that has occurred in birds is from the Type A subspecies. The avian flu has historically been lethal and has caused many deaths worldwide.

The ‘H’ in H3N2 refers to hemagglutin which is a glycoprotein that binds the virus to the host cell. ‘N’ refers to neuraminidase which is an enzyme found on the surface of the influenza virus that enables the virus to be released from the host cell. The numbers that accompany H and N refer to subtypes of the virus.

There have been several strains that have been associated with pandemics. H1N1, H2N2 and H3N2 subtypes were avian based. Newer subtypes of H1N1 include the swine flu.

In 2013, the emergence of H7N9 in China has raised concern for another worldwide pandemic. H7N9 is an avian based subtype but it has been reported that transmission from person to person may have occurred. There is a much larger mortality rate associated with H7N9 than with other subtypes. In fact, nearly one third of those infected during a 2013 outbreak died from complications associated with the disease. Some infectious disease specialists and researchers have laid claim that N7N9 could cause a worldwide pandemic, similar to the last one seen in 1918 which caused over 100 million deaths.

The first case of H7N9 in North America was reported earlier this year. A Canadian citizen tested positive for the disease upon returning home from Hong Kong in late January.

The underlying source for H7N9 appears to be from infected chickens that has spread rapidly among several provinces in China. There has been very limited reports of human to human transmission. The World Health Organization (WHO) is calling H7N9 one of the most lethal viruses seen. A vaccine is currently in clinical trials.

References:

http://www.cdc.gov/flu/avianflu/h7n9-virus.htm

http://www.scmp.com/news/world/article/1693111/vancouver-woman-diagnosed-h7n9-bird-flu-after-flight-hong-kong

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Cardiomyopathy in Friedreich’s Ataxia

18th Sep 2015 Diseases, Friedreich's Ataxia

A recently published study conducted through the New York Veterans Affairs Medical Center in Albany, looked at the association between Friedreich’s Ataxia (FA) and cardiomyopathy. While FA is known as a neurological disease, the most common cause of death in FA patients is cardiomyopathy. By definition, cardiomyopathy is a disease in which the myocardium becomes weakened or stretched resulting in decreased ability to pump blood to the rest of the body. As this progresses, arrhythmias and heart failure may result.

The study focused on 28 autopsy heart tissue samples from patients with FA. Additionally, 10 tissue samples were taken from healthy controls. Multiple measurements were made including X-ray fluorescence (XRF) of iron and zinc within the ventricle walls and interventricular septum, tissue frataxin, iron histochemistry, inductively-coupled plasma optical emission spectrometry (ICP-OES), and immunofluorescence of inflammatory markers hepcidin and CD68. Prior studies have focused on abnormalities related to left ventricular hypertrophy, dysfunction, and electrical abnormalities.

The tissue samples from hearts from FA patients showed evidence of hypertrophy and thickened walls. Muscle cells, known as cardiomyocytes were identified to be considerably larger in the control hearts. Additionally, the cardiomyocytes were surrounded by a layer of endomysium (fibrous connective tissue).

Further analysis of the tissue samples revealed a significant reduction in cardiac frataxin levels and higher levels of iron within the left ventricular wall and septum in FA patients. Furthermore, an abnormal number of CD68 reactive inflammatory cells was found in the hearts of FA patients. Cytosolic ferritin sequesters and stores iron to protect against free radical damage while hepcidin is a protein that plays a major role in iron regulation. Both of these markers were elevated in FA. The results of this study point have lead the researchers to believe that a strong iron expression seen in the cardiomyocytes might be a unique finding for cardiomyopathy in FA hearts. Since frataxin levels were low, the restoration of this mitochondrial protein and targeted anti-inflammatory therapy may be beneficial for those with FA.

The study was funded by the Friedrich’s Ataxia Research Alliance (FARA), National Ataxia Foundation, and the National Institutes of Health

References:

Koeppen AH, Ramirez RL, Becker AB, Bjork ST et al. The Pathogenesis of Cardiomyopathy in Friedreich Ataxia. PloS One. 2015 Mar 4;10(3).

Alboliras ET, Shub C, Gomez MR, Edwards WD. Spectrum of Cardiac Involvement in Friedreich’s Ataxia: Clinical electrocardiographic and echocardiographic observations. American Journal of Cardiology. 1986 Sept 58(6): 518-524.

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Predictors of disability among military personnel following a traumatic blast concussion

10th Sep 2015 Medical News

It is no surprise that military personnel who suffer a blast related brain injury are likely to experience post-traumatic stress disorder (PTSD) and depression. A recently published study out of the University of Washington in St. Louis has shown that when these early symptoms, which include anxiety, depression, flashbacks, and PTSD, occur within one week of the injury, they are a better predictor of long term disability than the results of common tests such as memory, thinking, and balance.

The prospective, observational study enrolled 38 U.S. military members who sustained a concussive traumatic brain injury. They were compared with 34 controls. All subjects who suffered injury were evaluated within 7 days at two sites in Afghanistan. The subjects were also re-evaluated again between 6 and 12 months post injury in the U.S. Service member’s ages ranged from 19 to 44 years old. Mental health was evaluated using a standardized military post-traumatic stress disorder questionnaire. Depressive symptoms and post-traumatic stress symptoms were elevated during the initial assessments while cognitive function was worse in subjects with a traumatic concussive injury. After the 6 – 12 month assessments, 63% of the subjects had moderate overall disability versus 20% in the control group. Moderate disability in this case is defined by inability to work in the same capacity as prior to injury, are unable to engage in normal social or leisure activities, and/or have disrupted relationships secondary to mental health disturbances.

It was believed that traditional measures including memory, attention, balance, and coordination would be the best predictors of long term disability. In this study these measures were not correlated with outcomes, but rather the psychological symptoms that were better predictors. It is unknown whether the psychological symptoms result from the brain injury, from stress related to war, or from other combined factors.

Having the knowledge that symptoms of PTSD and depression start much sooner than suspected in some cases, psychological evaluations should begin earlier and allow for earlier targeted care. The long term effect of this is unknown, but may offer the best chance to improve the quality of life. Researchers from the study also are planning to apply these findings in future studies looking at concussive brain injuries in the civilian world.

This study was conducted by investigators at the University of Washington in St. Louis and The U.S. Naval Medical Center in Portsmouth, Virginia.

References:

MacDonald CL, Adam OR, Johnson AM, Nelson EC, Werner NJ, Rivet DJ, Brody DL. Acute post-traumatic stress symptoms and age predict outcome in military blast concussion. Brain. 2015 Mar 4.

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Sequencing of common antibiotics may prevent drug resistant bacteria

04th Sep 2015 Diseases

Drug-resistant bacteria has become widespread. The World Health Organization (WHO) in 2014 made a plea for nations to monitor antibiotic resistance as there are serious public health consequences that can beginning to occur. A global survey showed alarmingly high rates of drug-resistant E-Coli and other bacteria that are capable of causing serious infections.

A recent study published by an international team based out of the University of Exeter in the UK has shown that alternating common antibiotics may prevent drug resistance. For many years, researchers have focused on using a combination of antibiotics as ‘cocktails’ with the thinking that a synergistic combination may be one answer to this growing problem.

In this recent study, the investigators used erythromycin and doxycycline to treat a test-tube model of resistant E-Coli. The antibiotics were given individually, in combination, and then in sequence. When given in certain sequences, they found that the infection was cleared. In most cases, the antibiotics given individually or combined failed to work. The researchers believe that specific doses of antibiotics combined with a specific sequence can make the bacteria sensitive and reduce risk of resistance.

As this was an experimental model, further research is needed to look at different combinations of drugs, doses and sequences.

Only two new classes of antibiotics have been introduced in the last 30 years. There is an urgent need to develop new drugs and while at the same time minimizing the prescribing and over utilization of antibiotics. Recently, the CDC announced that a drug-resistant form of the bacteria Shigella has caused illness in over 240 people since May 2014. 90% of the samples tested were resistant to the antibiotic Cipro. With more than 2 million cases of antibiotic resistant infections in the U.S. annually, rapid development of technologies to identify and characterize resistant bacteria has become a priority.

References:

Fuentes-Hernandez A., Plucain J., Gori F., et al. Using a sequential regimen to eliminate bacteria at sublethal antibiotic dosages. PLOS Biology. 2015 April 8;13 (4).

National Action Plan for Combating Antibiotic-Resistant Bacteria- https://www.whitehouse.gov/sites/default/files/docs/national_action_plan_for_combating_antibotic-resistant_bacteria.pdf

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