Randall the red-nosed toddler...

To the tune of Rudolph the red-nosed reindeer

Randall the red-nosed toddler
Had a very runny nose 
Asthma exacerbation 
Fever adding to his woes 

All of the other toddlers 
Didn't have immunity 
They all came down with symptoms 
Differing in severity 

Then one group of researchers 
Virus-hunting was their game 
Swabbed, extracted, amplified
A rhino POS of course was spied 

Randall�s rhino was sequenced 
Turned out to be rhino C
Randall the red-nosed toddler
Just a 'common' cold indeed!

Randall the red-nosed toddler

Had a very runny nose 
Asthma exacerbation 
Fever adding to his woes 


Thanks to Katherine Arden and Cassandra Faux for helping me put these together back in 2008.

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More confirmation that rapid influenza diagnostic tests (RIDTs) should be used in context

The Texas Department of State Health Services have a useful couple of paragraphs from an Influenza Health Alert that puts into context reliance on the convenient and rapid, but ultimately intensive rapid influenza tests.

Rapid Lab Tests: Rapid Influenza Diagnostic Tests (RIDTs) can be useful to identify influenza virus infection, but false negative test results are common during influenza season. Clinicians should be aware that a negative RIDT result does NOT exclude a diagnosis of influenza in a patient with suspected influenza. When there is clinical suspicion of influenza and antiviral treatment is indicated, antiviral treatment should be started as soon as possible, even if the result of the RIDT is negative, without waiting for results of additional influenza testing.

Mike Coston also has an excellent article touching on some of the many other viruses that can cause influenza-like illness and on rapid testing, over on his blog, Avian Flu Diary. I highly recommend it.

Cost is always an important factor when hospitals and attached diagnostic laboratories consider how to address infections. Rapid turnaround time is another major cost because, for those small number of viruses with this option available, an antiviral drug can be administered and there seem to be benefits from doing this as early as possible for severe influenza. In some cases of course, a vaccine is available to block severe disease from occurring when you get infected (they don't stop infection, but a response to a vaccine is much safer than a bad response to an actual virus infection, as we've seen in the recent media for H1N1 in Texas. 

During flu season, influenza virus is an obvious cause for a spike in hospital admissions for acute respiratory symptoms - but if confirmation of that pathogen relies on a testing platform that can miss a third of infected individuals (only 17/45 PCR positives were detected by am RIDT in Ref#2) then antivirals may not be used in time. In a more recent comparison of RIDTs using PCR results as the standard, viral load in the upper airway (less virus gave fewer positives - duh), age (the young and elderly were less often positive), presentation time (sampling >2-days after onset of illness reduced the proportion of positivity), virus type (less sensitive for subtype B infections than A) and whether there was pneumonia or not (the former were less often positive perhaps reflecting less viral replication in the upper airway than in the lower airway?) were factors in how well the antibody-based RIDTs performed. Sensitivity ranged from 50% to 94%. These 2 studies used samples from the upper airways (swabs or nasopharyngeal aspirates respectively, as suggested by the BD� Directigen EX Flu A+B assay, Alere� Influenza A & B Test and the QuickVue� 117 Influenza A+B test)

In these instances, PCR-based methods (used as the "gold standard" in those published evaluations) shine but they take longer to generate a result and require more expertise to conduct than a rapid test. The slightly longer time is not just because they take hours to conduct instead of the minutes of a rapid test (remembering that viral lab diagnoses used to take days not hours) but because lab testing is only part of a process which also involves paperwork and passing verified and signed off results and information to all concerned clicnial parties and patients. That can take more time-and sometimes be a bottleneck for result release. Its hard for a patient's family and friends to wait, but the results will be that much more reliable when they come.

A feature of influenza season is the concurrently reduced levels of activity of other viruses. Influenza tends to "push out" a lot of other viruses during it's peak season - probably reflecting influenza's ability to dominate the immune response in an infected individual, and by extrapolation, reduces the number of susceptible individuals at the community level, remembering that the majority of influenza cases are acute upper respiratory tract illnesses.

So it looks more like the Montgomery County deaths may have been due to the high levels of influenza A(H1N1)pdm09 virus generally circulating in them there parts. A KHOU news outlet report, also circulated on ProMED, suggest that 4 Montgomery county deaths were due to H1N1, as well as other sine the regions. However, the Montgomery County Public Health District reports only 2 H1N1-confirmed deaths, so things are still a little confusing there. And as for whet other viruses may also be in these patients...so far, who knows?


A brief guide to some terms used in these sorts of discussions (also from Ref #2 below)

Sensitivity
No. of true positives / no of true positives and false negatives

Specificity
No. of true negatives / no of true negatives and false positives

Positive predictive value
No. of true positives / no of true positives plus no. of false positives

Negative predictive value
No. of true negatives/ no of true negatives


References and further reading...

1. FluTrackers story. http://www.flutrackers.com/forum/showthread.php?p=517368#post517368
2. Accuracy of rapid influenza diagnostic test and immunofluorescence assay compared to real time RT-PCR in children with influenza A(H1N1)pdm09 infection. http://www.ncbi.nlm.nih.gov/pubmed/23175329
3. Clinical and Virologic Factors Associated with Reduced Sensitivity of Rapid Influenza Diagnostic Tests in Hospitalized Elderly and Young Children. http://www.ncbi.nlm.nih.gov/pubmed/24285739

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Texan flu step: flu-like illness outbreak in Montgomery County [UPDATE #2]

Click image to enlarge.
County of Montgomery highlighted in red.
From Wikipedia

While 1,920 influenza-like illnesses (briefly that's measurable fever plus one or more particular symptom usually; includes sore throat, fatigue, body aches and complications including pneumonia) have occurred in this county since the start of the local influenza season, 8 severe infections (all with pneumonia) in adults (41-years to 65-years old) have been admitted to 1 (?) facility. These 8 cases are not all testing positive for the "common" influenza virus types. Initial testing may have been by rapid "bedside" influenza test which are known for their lack of sensitivity. PCR testing would be preferred, if that wasn't used.


According to the US Centers for Disease Control and Prevention website, seasonal influenza's populations at greatest risk of severe disease usually include the very young (under 5-years) and older adults (>65-years), pregnant women and indigenous populations, and those with a range of pre-existing medical conditions.

4/8 cases died and none of the fatal cases were vaccinated against influenza (?survivors were vaccinated). Kidney issues have also been reported according to a video report at the Houston Chronicle.

1/4 surviving case has tested positive for influenza A(H1N1)pdm09 virus, which is circulating locally as the annual flu season is well engaged in the region. 2 other survivors have tested NEG for all influenza viruses and have been sent on to the CDC. Test results are outstanding on the other survivor.

Click on image to enlarge.
2013-14 Influenza season data from FluView, CDC at
http://gis.cdc.gov/grasp/fluview/main.html.
Of those 221 antigenically subtyped by the CDC,
184 are H1N1 2009.

Management steps include staying away from ill people, hand-washing using soap and water/alcohol-based hand rubs, covering coughs and sneezes, staying at home when ill, cleaning linens, eating utensils and dishes used by ill people, and wiping down frequently touched surfaces if likely to be a landing spot for virus from an ill co-habitant/co-worker/school or daycare child.

It would be interesting to know what testing has been employed for influenza and what other respiratory viruses and bacteria have been tested for and excluded because, despite some enthusiastic but highly misleading and inflammatory guesswork, there are not yet enough data to identify an infectious aetiology for this pneumonia cluster. I'm sure in a busy environment like this, work is progressing on many levels to resolve the mystery. Since at least 2 of the 8 patients have tested negative for influenza viruses, it is premature to extrapolate from the 1 positive case that H1N1 is the cause of all cases; it may be but those results are not yet in.

References...

• CIDRAP story. http://www.cidrap.umn.edu/news-perspective/2013/12/texas-health-officials-probe-severe-flu-illness-cluster
• Montgomery County Public Health on Facebook page. https://www.facebook.com/mctxpublichealth
• FluTrackers page. http://www.flutrackers.com/forum/showthread.php?t=214964
• Fox Houston. http://www.myfoxhouston.com/story/24257668/the-return-of-h1n1

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Influenza A (H10N8) virus, the new kid on the block...

Click on image to enlarge.

Step by step we seem to be getting familiar with the entire influenza spectrum of naming combinations and permutations. When you consider that even 2 influenza viruses with the same common naming scheme (like H7N9) may have completely different evolutionary histories and clinical impact, well, influenza is a tough act to follow epidemiologically.

The latest, called H10N8 was detected in a human (73-year old female) for the first time Dec-6th. H10N8 has been found in the environment in the past.

The woman, who had visited a live bird market, died from respiratory failure following pneumonia, although whether that was due to H10N8 infection is not clear. The woman was treated in hospital in Nanchang, Jiangxi province from Nov-30; she also suffered a heart attack, was immunocompromised, had high blood pressure and a neuromuscular disorder.

Hong Kong's Centre for Health Protection (CHP) urged travellers to stay away from live bird markets and to avoid contact with the birds/poultry and droppings.


As CIDRAP noted, low pathogenicity avian influenza A(H10N7) virus has been reported in 2 Australian adults processing chickens during an outbreak of the virus in 2010 and reported in 2 Egyptian infants (1-year old) possibly linked to market ducks during late April 2004.

h/t to crofsblog and CIDRAP.

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A new rhino type is coming to town...[corrected]

To the tune of Santa Claus is coming to town

You better watch out
No need to try
Taking antibiotics
I'm telling you why
New rhino types have come in to town (Don't gather 'round)

It's making a list
Not sickening you twice
Will get to you if you're naughty or nice 
New rhino types have come in to town 


Infects you when you're sleeping
Infects if you're awake
Can make you crook and wheeze a lot
Not so "common" for goodness sake!


O! You better watch out!
No need to try
Taking antibiotics
I'm telling you why
New rhino types have come in to town 

___

This one's a bit old now, but came about during our work in defining the third rhinovirus ("common cold" virus) species, RV-C.

Thanks to Katherine Arden and Cassandra Faux for helping me put these together back in 2008.

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EMERGENCY NEEDS ASSESSMENT IN WESTERN KENYA

Hello again from Western Kenya. As I conclude my trip, I wanted to update everyone on the status of the project. It's been a wild 6 weeks, full of travel. We were able to visit 27 facilities in total - learning a great deal from all of the wonderful medical providers who gave their time to help in this project.

Not surprisingly, we've discovered there is definite room for improvement for emergency care in Western Kenya. Finding out how we can focus our efforts best will be the greatest challenge. We have found that even basic supplies like X-ray and ECG machines are lacking, the providers (especially specialists) are frequently overworked and spread-thin, referring patient's to a higher level of care poses many challenges and can be dangerous, and many providers are requesting more trainings to be able to take care of their patients better.

I was able to pass the torch to another fellow resident who will continue collecting data. When complete, we will analyze our data and work with local medical officials to raise the standards of emergency care in the region. Fortunately, we've already started a pilot training program to train some providers on emergency anesthesia.

Dave Young, MD

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