Showing posts with label United States of America. Show all posts
Showing posts with label United States of America. Show all posts

Saturday, 31 January 2015

The filovirus tree has been shooting wildly

While there are not a lot of new branches, there are many, many new leaves on this growing tree. That is overwhelmingly due to the fantastic work of Dr Pardis Sabeti, and Stephen Gire at the Sabeti lab, Harvard University, and their many collaborators. 

It sounds like even more sequences will be coming out in the future. This group is the face of the molecular epidemiology of history's largest Ebola virus disease epidemic in Sierra Leone. If a team of scientists could be said to embody an aspect of an epidemic, it has been these guys and their virus characterization. Hugely impressive stuff.

I only wish we could see more Guinean and Liberian sequences - they are both hugely under-represented in this tree of complete genomes downloaded from GenBank a week or so ago.

Click on tree to enlarge even further.
Coloured boxes surround those sequences generated during the
2014 EVD epidemic. Orange boxes point out the nearest neighbours
and the year from which the sample that was sequenced, originated.
The West African Ebola virus Makona variant has been
traced back to sharing an ancestor in common with a 2007
variant in 2004.

References
  1. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Gire SK, Goba A, Andersen KG, Sealfon RS, Park DJ, Kanneh L, Jalloh S, Momoh M, Fullah M, Dudas G, Wohl S, Moses LM, Yozwiak NL, Winnicki S, Matranga CB, Malboeuf CM, Qu J, Gladden AD, Schaffner SF, Yang X, Jiang PP, Nekoui M, Colubri A, Coomber MR, Fonnie M, Moigboi A, Gbakie M, Kamara FK, Tucker V, Konuwa E, Saffa S, Sellu J, Jalloh AA, Kovoma A, Koninga J, Mustapha I, Kargbo K, Foday M, Yillah M, Kanneh F, Robert W, Massally JL, Chapman SB, Bochicchio J, Murphy C, Nusbaum C, Young S, Birren BW, Grant DS, Scheiffelin JS, Lander ES, Happi C, Gevao SM, Gnirke A, Rambaut A, Garry RF, Khan SH, Sabeti PC.
    Science. 2014 Sep 12;345(6202):1369-72. doi: 10.1126/science.1259657. Epub 2014 Aug 28.

Wednesday, 1 October 2014

The United States of America is the 6th country to host a 2014 West African Ebola virus variant..

v4 08102014 07:00am AEST
First thing...
CALM DOWN!

This (announced 30-Sept) is the first case of Ebola virus infection to arrive in the United States that was not deliberately flown in. Its not the first viral haemorrhagic fever case though (1 case of Marburg virus disease and at least 4 Lassa virus infections and the Reston ebolavirus outbreak among imported animals[3,5]), and none of the earlier infections resulted in secondary transmission among humans; no-one else got infected from by the case.[4]
Countries that have hosted people infected
with the Ebola virus variant causing the
& 2014 West African Ebola virus
disease epidemic.
Click on image to enlarge.

The male is in critical condition.
When he flew from Liberia to the United States (finally arriving in Dallas,Texas). The man was not showing signs of disease when leaving Liberia or on the plane or immediately after arriving.[6]

This means that the man was not infectious - he could not spread it to fellow travellers or airport workers - because it is well known that disease in another does not develop due to virus being shed before disease is obvious in the infected person.

Briefly[1,2]:
  • 19th: Departed Liberia, checked and found to be symptom-free
  • 20th: Arrived in Dallas, US (Brussels to Washington on United Airlines 951, then to Dallas Fort Worth on 822 [7])
  • 24th: Started to develop symptoms
  • 26th: Initially sought care for fever and abdominal pain (not vomiting). Sent home with antibiotics.[8]
  • 28th: Admitted to Texas Health Presbyterian hospital in Dallas, Texas. Vomited as leaving home to get into ambulance.
  • 30th: Texas public health laboratory found Ebola virus this morning of 30th Sept. CDC received samples, tested and confirmed as Ebola virus disease
  • 1st Oct: WHO announced case
  • Patient is ill and is under intensive care

US family and community contacts (a "handful") are known or being traced and will be under observation/monitoring for 21-days (~21-Oct) for fever. Will any become positive for Ebola virus? Perhaps. I look to Port Harcourt (Nigeria) for some comfort. There were around 60 "high risk" contacts of there and they did not all become ill.

The man identified his country of recent origin, Liberia-the country carrying more cases of Ebola virus disease than any other in history, to a triage nurse on the 26th when he first reported to the Texas Health Presbyterian Hospital. That the information was not passed along sufficiently.[7] While the signs and symptoms were non-specific-all sorts of infectious agents could cause fever and gut issues-the travel history should have been a very important red flag. 

He was sent home with antibiotics. Many acute febrile illnesses are viral  in nature, and antibiotics do not treat viral infections, just bacterial ones but do a great job at helping out antibiotic resistance. Sigh.

So now we have evidence that supports all those talking heads (me included) who noted that it was possible for sporadic cases of EVD to be imported into countries outside of those in West Africa (Guinea, Liberia, Sierra Leone, Nigeria, Senegal). It also, sadly, shows how human infectious disease are - literally by infecting us and using us to cough, vomit and bleed the bug onto to another person, but also figuratively in the roles we play in helping that spread to happen.

Soon, I very much believe, we will also have evidence that in richer countries with functioning healthcare systems, a good knowledge of what is needed to contain virus infections spread by all possible routes, stocks of the necessary personal protective equipment needed to protect healthcare workers from nosocomial infections and the training to use those stocks...that even when unexpected Ebola virus disease cases arrive or incubate and emerge, they will not result in outbreaks.

References...
  1. https://www.youtube.com/watch?v=6Bxencye1cg&feature=youtu.be
  2. http://www.nytimes.com/2014/10/01/health/airline-passenger-with-ebola-is-under-treatment-in-dallas.html?partner=rss&emc=rss&smid=tw-nytimes
  3. http://scienceblogs.com/aetiology/2014/08/02/ebola-is-already-in-the-united-states/.
  4. http://blogs.scientificamerican.com/molecules-to-medicine/2014/09/30/ebola-in-usno-need-to-panic/?WT.mc_id=SA_sharetool_Twitter
  5. http://www.cdc.gov/media/releases/2014/s930-ebola-confirmed-case.html
  6. http://news.sciencemag.org/health/2014/09/one-more-ebola-question-dr-frieden-answers-journalists-would-have-first-u-s-case?rss=1
  7. http://www.usatoday.com/story/news/nation/2014/10/01/hospital-ebola-patient/16527143/
  8. http://www.usatoday.com/story/news/nation/2014/10/01/texas-ebola-patient/16525649/

Thursday, 29 May 2014

Updated MERS map moves stars around....

This new version adds a blue star to Iran, as it seems likely there has been some local transmission. 

That star has been taken away from the USA (it's been a bad boy) since there has now been no sign of local transmission after the overnight retraction of the Illinois man's positive antibody test result.

Click on image to enlarge.

Tuesday, 20 May 2014

MERS-CoV detections: The April wave recedes...

So welcome to the 114th Week of MERS-CoV among us. That week numbering may change shortly. Stay tuned if week numbering is your thing.

We currently have a tally of 649 detections of MERS-CoV or viral antibodies in humans. I don't list camel numbers. My count says 192 fatalities among infected people, resulting in a proportion of fatal cases of 29.6%. That seems high. Because, until very recently, the Kingdom of Saudi Arabia's Ministry of Health did not regularly report deaths alongside their date of illness onset, it has been an interesting hobby to try and link them. The number is solid so along as the MOH has not been doubling up in the reporting or coming back later to re-report deaths. You'll be familiar with these issues if you follow me on Twitter.

I made a point of saying antibodies earlier because I am going to be including these sorts of laboratory data in my tally when produced by trustworthy laboratories who have described their methods and shown some validation data and an understanding of what the cross-reaction issues are when dealing with MERS-CoV serology. This will be despite the current WHO MERS case definition not allowing for inclusion of people who only have antibody but no virus or viral RNA detected in their samples. There may be some hiccups with MERS-CoV antibody testing along the way, but we need these data in humans and it's good to see the wheels rolling on this at last.
[One of those hiccups occurred 28-May-2014, when the test result from an Illinois man who had originally tested positive in an Ab test, was retracted.]

In my estimation though, serology (the testing of human sera for antibodies against a virus here, the main target being IgG which takes a couple of weeks to become detectable after infection) is a much more reliable way of defining an infection by MERS-CoV virus than by relying on patient recall bias of symptoms 2-weeks ago, or from directly observing signs and symptoms that are nondescript and difficult to distinguish, alone. The latter approach has been the mainstay of identifying cases of human infection for a very long time; still is. This approach is especially important during times of outbreak and pandemic when labs are swamped by testing requests and it must be assumed that cases are due to the bug of interest; if it looks like a camel, slobbers like a duck and walks like a duck, then it is a MERS-CoV infection yeah? No. If you can clinically characterise and laboratory test then you will more often know the virus the patient has/had than if you don't test. But I'm sure that's clear to everyone anyway.

For MERS, as for H1N1pdm09 influenza and perhaps SARS, finding a reliable pathognomonic set of signs or symptoms capable of reliably distinguishing a respiratory virus of interest from another virus capable of the same disease is not possible. These viruses cause a spectrum of illness. Testing is paramount if you want to know what's there and to address other aspects relevant to public health during an infectious disease cluster/outbreak/pandemic. There are a couple of issues here (at least!)...

From a patient management perspective, who really cares what is making my patient very ill anyway? It really doesn't matter right now if it's this respiratory virus or that one; there are few vaccines and I don't have an antiviral for most of them anyway. I and my healthcare team are already taking respiratory infection precautions and I just want to direct my supportive therapy and resources to the problems they have, right? I'll be (well...you, experienced medical types of which I am not one) doing that before many lab results show up anyway. 

From the perspective of interrupting and understanding viral transmission however, nondescript signs and symptoms are a nightmare. And in the early days of a new virus where we seem to know very little about what path(s) transmission is taking (and perhaps we're also learning some more about those possibilities in general), any infection by whatever method it is empirically determined should, I believe, be recorded as an infection in order to provide the biggest picture possible; a process we have seen unfolding in the United States with its 2 3 detections (1 locally transmitted) of MERS-CoV or its spiky little footprints.
THIS RESULT WAS RETRACTED 28-May-2014 FOLLOWING A NEGATIVE NEUTRALIZING ANTIBODY TESTING.

Given that many viruses cannot be distinguished by signs and symptoms alone, a clinical diagnosis to define a case is less reliable than any pathogen-specific laboratory test. I hope the WHO alters their case definition in the near future. Infectious disease is always teaching us - seems we learned a heap from SARS but even the relatively a few cases of MERS are presenting interesting issues and testing us in new ways. 
[While the US antibody-positive result above has since been retracted, I stand by these comments-Ab testing requires rigor, but that can be provided using several assays and applying a good understanding of Ab technologies and limitations to produce reliable results]

Anyhooooo...been stewing on that for a few days apparently. Let's move on and have a look at the 3 updated charts below. 

We are definitely through to the other side of the Jeddah outbreak (see weeklies chart). While cases do keep accruing each and every day (see dailies chart from 20-March), the downward trend of smaller numbers of illness onsets each day also continues. 

Weekly MERS-CoV detections.
Click to enlarge.

Daily MERS-CoV detections from 20-March.
Click to enlarge.

For perspective on the size and the influence of what 1 hospital cluster can turn into and how that can influence how a virus "looks", take a gander at the extent of the April outbreak. Case are still falling out into April as we get more data. If you look at the monthlies chart at the bottom, I've readjusted that y-axis scale again such that it's maximum value is now 10x higher (350 vs 35) than the scale used for 2012 or 2013's charts. May's tally is currently 4x greater than any month from 2012 or 2013. 

What does MERS-CoV hold for us in the coming months? 

Daily detections of MERS-CoV, 2012-current.
Click to enlarge. 

Monthly detection of MERS-CoV 2012-current.
Click to enlarge.


Wednesday, 14 May 2014

Keep calm and call the lab...without it, you know less than you think you do [UPDATED x2]

This morning there are 2 symptomatic healthcare workers (HCWs) in the United States (of America; I'm just going to use the "US" from from here on) who came into contact with the recently diagnosed MERS-CoV positive 44M (age and sex confirmed yet?) imported case.

The news has driven something of a twitter storm in the #MERS channel. Not unexpected I guess. The implication is that these 2 have acquired MERS-CoV from contact with the imported MERS-CoV-positive person. 

But that link is still far from proven yet. [UPDATE: both HCWs tested negative for MERS-CoV [1]]

This is a slightly revised version of that which I posted 18-March.
Thanks to Dr K Arden for helpful advice.
Click on image to enlarge.
VDU images are free to re-use. I can provide a better quality if needed.
Please just cite Dr Ian M Mackay, and this blog, http://virologydownunder.blogspot.com.au/,

if used elsewhere.
...Something to remember, or become aware of...

There are >200 known human viruses that have at one time or another been linked to patients with signs and symptoms that defined an 'influenza-like illness" (ILI). No-one can predict what these HCWs are infected with, but they have been or currently are infected by something. Lab tests are essential to know this.

I've asked Orlando Health's social media team (@orlandohealth) if these 2 HCWs are also being tested for the more "standard" 8 or 9 endemic human respiratory viruses/virus groups in parallel with MERS-CoV testing. I'll update this post with what I learn.

These standard viruses include influenzaviruses (A and B; red above), respiratory syncytial virus (dark pink), adenoviruses (orange), human metapneumovirus (pale pink) and parainfluenzaviruses 1, 2, 3 (purple). I'd also hope the rhinoviruses (in green above) since they are numerous and a frequent cause of ILI that can confound the very broad ILI tag. This panel of viruses comprise a standard testing menu which may be further extended, or shrunk, depending on the lab and they are included in commercial PCR-based kits. 

Keep in mind too that a positive PCR (if that's what is used) result does not mean the virus found is the cause of the illness. It may be that another virus, that has since dropped below the limit of assay detection was the cause, or a couple of viruses working in series or parallel, or a virus & bacterium working in synergy or a virus that wasn't tested for, or a virus that is not even known yet...pant.

But if these 2 HCWs do test positive for the MERS-CoV, it's not all that unexpected. Respiratory viruses on the scale you see above have not co-evolved with us/been introduced to us recently because they are easy to get rid of or stop from spreading between/to us.

MERS-CoV is just one of a long line of (probable) respiratory viruses that keep taking us to school to teach us just how sneaky and effective they can be at spreading and just how much our preconceptions trip us up, letting them finish with the best grade.

To stop the spread of them in an environment full of sick people, like a hospital, or even a school, a daycare centre, a long term care facility, a cruise ship, a plane, bus, or even a living room, is no mean feat. It's worth remembering that no single virus does only one thing. There is no "pneumonia virus", no "bronchitis virus", there's not a "common cold virus", there's no "droplet-only" spread, there's not "only replicates in nasal cells", there are just respiratory viruses and their very complex multicellular hosts. I'm happy to argue any of these points, but come prepared to show me that every avenue has been exhausted to support your argument beforehand. I'll give you the drum right now, they really haven't.

Respiratory viruses can each do lots of things and the outcome on our health is heavily determined by usour previous exposures, our age, our general health, our maternal antibody levels, our underlying diseases, our genetic makeup, our environment, our climate, our animal and human contacts, our personal hygiene and our habits.

End of monologue.

Reference...

  1. http://www.flutrackers.com/forum/showpost.php?p=534975&postcount=49

Sunday, 4 May 2014

MERS in the USA....

The source of all exported MERS-CoV positive people lies within the Arabian peninsula. Very limited local spread has occurred within 3 non-peninsula countries.
Click on image to enlarge.

The Middle East respiratory syndrome coronavirus (MERS-CoV) made its way to another country yesterday; the United States of America (USA).


MERS-CoV in the KSA during April.
Filled red circles mark towns and cities for general interest.
The darker sandy coloured areas indicate KSA Regions
(also Egypt and the United Arab EMirates) where
MERS-CoV detections have been located recently.
Click on image to enlarge.
This is not a big surprise and it's not the end of days, but dude...it lit up Twitter and had reporters high-five'ing like nothing the 460 cases before it, mostly around the Arabian peninsula, managed to achieve. But then MERS-CoV detections have only been accruing for 111 weeks. 

These things can take time to warm up.

The USA case was in a healthcare worker (HCW) travelling back from the Kingdom of Saudi Arabia (KSA).

What else do we know?

  • FluTrackers #456
  • The HCW who was working in Riyadh, KSA, travelled back from there to Chicago in the USA via a transfer at Heathrow airport in the United Kingdom, 24-Apr.
  • Illness became more noticeable 27-Apr (coughing, shortness of breath and fever), and the person was hospitalized 28-Apr in Indiana.
    Was less noticeable illness present first? We know little about what the earliest inklings that someone has a MERS-CoV passenger feel/look/sound like.
  • Age and sex of the patient have not been officially released.
    I should stop complaining about that from the KSA Ministry of Health data. Still important to know it, but if its not provided by one high income economy, why expect it to be provided by any other?
  • The laboratory confirmation was made 2-May (~4-days)
Because the person wasn't coughing, sneezing or noticeably wheezing on the planes, it will be unlikely that any virus was propelled towards, or impacted upon surfaces shared by, people nearby. We will of course be watching as the USA health professionals track, observe and hopefully swab and test at least some of the contacts from the planes and post-transit spaces. These people can tell us a lot about what the virus is doing among people not defined as "close" contacts; a kind of live experiment to check if MERS-CoV transmits any differently now than it did the last time it got loose from the Arabian peninsula. On those recent occasions neither Greece, Malaysia nor the Philippines saw any additions to the transmission chain.

I can remember when MERS and H7N9 cases were so rare I used to do a work up like this on each announcement. Ahh the good old (slow) days.

Sources...

  1. http://www.cdc.gov/media/releases/2014/p0502-US-MERS.html
  2. http://www.in.gov/activecalendar/EventList.aspx?fromdate=5/1/2014&todate=5/31/2014&display=Month&type=public&eventidn=169819&view=EventDetails&information_id=200566&print=print

Thursday, 19 December 2013

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...

Thursday, 23 May 2013

"Mystery" respiratory illness in Alabama, US.

The past couple of days has seen many reports on a growing number of cases of cluster of acute respiratory illness. The Alabama Dept of Public Health (ADPH) issued an alert yesterday requesting that care providers to be on the lookout for unexplained case of pneumonia.

Cases of interest present with fever, cough, shortness of breath and "something" on their chest x-rays. Upper airway swabs or aspirates have been requested from such cases, regardless of "quick flu" test results. To date, samples have been collected and sent to local labs and to the US CDC.

A total of 10 cases - including 2 deaths (30-40y of age ) - are yet to be linked to a suspected pathogen and are not epidemiologically linked to one another.
Two cases positive for influenza (H1N1 and a seasonal H3) have already been reported (rapid antigen point of care testing?) although the flu season is currently winding down in the US. Two patients have already been discharged.

The cluster of respiratory illness can be traced back to around April 19th. Preliminary testing results should be arriving from the CDC soon.

FluTrackers are keeping a close eye on every report here.