Showing posts with label infection. Show all posts
Showing posts with label infection. Show all posts

Saturday, 26 April 2014

MERS is a respiratory disease and MERS-CoV is a respiratory virus... PART I

The disease

Definition time.

The Middle East respiratory syndrome (MERS) is a disease (a change in the body away from normal function towards abnormal function) comprised of a bunch of signs and symptoms (the syndrome bit) that is identified in patients who turn up ("present") to their doctor/clinic/hospital with signs (things the doctor can see or measure e.g. coughing, sneezing or a fever with a temperature about 38°C) and symptoms (things the doctor can't see that may still be measurable or not e.g. lung inflammation upon X-Ray, muscle aches or chills but no measurable fever).
 

At the bad end of the disease spectrum, MERS is an acute community-acquired pneumonia (CAP; confirmed by X-Ray of the lungs) that progresses to be worse. "Worse" includes kidney failure acute respiratory distress syndrome, respiratory failure and multi-organ failure. MERS pneumonia cannot be told apart from acute CAP due to other causes.

Laboratory testing to confirm the presence of the agent you suspect, is essential. You can't confirm its absence, but you can say it was "not detected".
 

MERS is a particularly nasty disease for those who already have a disease that is chronic. These include diabetes, kidney disease, heart disease, hypertension, lung disease, obesity, malignancy and those who smoke or use steroids. This appears to more often include older males around the Arabian peninsula in whom the coronavirus that is assumed to cause MERS (MERS-CoV), has had a big impact, associated with the most severe forms of the disease and death. Neonates, infants, toddlers and children (up to 14-years) are in the minority of MERS-CoV detection to date (14 of 361 with age data, or 3.9%).

Over 85% of patients with MERS (remember: the disease, not the virus) have a fever >38°C, cough and chills or rigors (shaking episode) and all have an abnormal 1st chest X-Ray.

Around half have a runny nose and about a third have malaise (feel rubbish) and myalgia (aching or sore muscles).

A quarter have diarrhoea and a fifth have sore throat, nausea or vomiting.[1]


The virus.

While it has not been shown conclusively in humans, the MERS-CoV has been shown to cause MERS or a similar, although milder form of disease, in Rhesus macaques given an unrealistically large and I would argue, unrealistically located (the trachea) dose of virus preparation. So we work under the assumption that the MERS-CoV causes the signs and symptoms listed above, and/or causes our immune system to respond in such a way that respiratory disease is what MERS causes.

We talk about MERS being caused by MERS-CoV.

We also talk about flu being caused by influenzaviruses. To confuse matters though, there is no single "common cold virus" that causes the common cold so we need to specify that common colds can be caused by any respiratory virus (there just happen to be more rhinoviruses than an other respiratory virus so they mistakenly wear the brunt of that burdensome label even though they are also the main viral cause of much more severe asthma attacks).


Breathing in versus ingesting.

The MERS-CoV presents first as an acute respiratory infection, with some other things that develop or are exacerbated (pre-existing diseases in particular).

Even when atypical disease presents first and respiratory disease follows, that may simply be explained by other preceding or concurrent infections. Take the recent Greek imported case of MERS from Jeddah, Saudi Arabia. He presented first in Saudi Arabia with fever and diarrhoea and was also subjected to an X-Ray and found not have no pneumonia. He had visited his wife in hospital there and she had been diagnosed with typhoid fever. He was also given antibiotics to combat that bacterium based on a positive test. He then travelled to Greece whereupon he presented to Athens hospital with fever and low blood oxygen levels indicative of viral pneumonia. That was confirmed by an X-Ray. This can be interpreted as an atypical presentation of MERS...or perhaps just MERS following typhoid or a even an acute viral gastroenteritis. Very little testing of faeces was described for the latter possibility and so we don't know. And into the void walks hand-waving.


Sources...

  1. Middle East Respiratory Syndrome Coronavirus (MERS-CoV): A Perpetual Challenge
    http://www.annsaudimed.net/index.php/vol33/vol33iss5/631.html
  2. A CASE OF IMPORTED MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS INFECTION AND PUBLIC HEALTH RESPONSE, GREECE, APRIL 2014
    http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20782

Sunday, 29 December 2013

What to watch for with human parechovirus (HPeV) infections...

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Friday, 11 October 2013

How mice lie....

In a nice 9:40 video presentation to TEDMED 2013, H. Shaw Warren brings us up to speed on some of the shortcomings of using mice to understand our complex human immune responses to bacterial infection.

Some key points he makes are:


  1. We use inbred mice. They "all look the same" because they are. That does not capture the diversity of responses to infection that we must deal with in trying to understand human infections
  2. Mice are resistant to infection and inflammation requiring lots of material o be injected. This is not what happens in the wild (100-100,000x more resistant than humans)
  3. Trauma and burns can be studied by examining gene responses in humans. These studies found poor correlation with mouse models.
  4. Mice look very different from us, why wouldn't their immune responses be equally different?
  5. Mice have evolved in environments rich in microbial exposures
  6. Mice have large litter sizes and short gestational periods which would increase adaptive evolutionary cycles - perhaps they have adapted to tolerate larger inocula than humans
  7. Mouse model success often determines whether a candidate drug proceeds to human trials. Some of these may work in humans
  8. All of the drugs studied in mice that have worked, have failed in humans (I did not know that)
  9. Mice still useful for gene, gene pathways, techniques and toxicity studies but extrapolating to complex human inflammatory disease networks may be a stretch
  10. The scientific community should raise the bar in justifying a link between human and mice responses before proceeding
Very nice talk.

Thanks to @MsWZ for tweeting link

Thursday, 27 June 2013