MERS-CoV snapdate on canaries...

MERS-CoV detections among healthcare workers (HCWs)

HCWs are akin to the canary in the coal mine - when HCWs get sick with a particular bug, this can signal that the bug may well be more active in the the wider community. 

This graph looks at the canaries and suggest that there has been a relatively long period in which they have been getting infected.

Healthcare workers positive for MERS-CoV over time.
Some reported or hypothesized clusters and outbreaks are flagged.
Click on image to enlarge.

A quick look at my database shows that most of the MERS-CoV-positive HCWs reported since October have been from Riyadh in Ar Riyadh region and Taif in Makkah region. 

Just before that, in early September, there were 2 HCWs from Jubail in the Ash Sharqiyah (eastern) region. 

If we look at the new time-based occurrence heatmap I have on my MERS-CoV static page here, the recent group of HCWs come from the areas with most cases. No big surprise there. Perhaps more surprising is why these HCWs are, presumably, still acquiring there infection in hospital settings given eh attention that infection prevention and control practices had, especially (before?) during and after the Jeddah outbreak last year.

A recent paper from Profs Drosten and Memish speaks to this topic of infection control and hospital spread of MERS-CoV a little.[1] 

It reports finding a 40-year old female (40F) nurse who, despite MERS-CoV being such a wimpy transmitter between humans, became infected after attending an infected patient. 40F did not perform any aerosol-generating procedures  but also wore only a surgical mask and gloves - it reads as though she was not fully protected against droplet, and certainly not against airborne, exposure. 

The 40F HCW then went on to shed virus for a 42-day period as determined by MERS-CoV specific RT-PCR. She was not ill during this time. Hard to contain much?

So with all that in mind, it's no longer hard to imagine how spread of MERS-CoV virus occurs within, around and between hospital settings. Also helps to explain how some of the new cases might seem strange - if not testing for subclinical or asymptomatic cases as a routine. I recall that in Saudi Arabia routine testing of milder cases is not occurring, but I cannot find a source for that recollection just now so I stand to be corrected (please send if you know if a reference that alludes to that).

A couple of quick questions spring to mind:

1. Just how widespread is this lengthy shedding period?
2. What does this say about how mild a virus MERS-CoV is when comorbidities are not a factor?
3. What role do genetics play in the host's containment and clearance of MERS-CoV infection?

Heatmap of MERS-CoV detection by date and region
within the Kingdom of Saudi Arabia
Click on image to enlarge.

Reference..

1. A Case of Long-term Excretion and Subclinical Infection With Middle East Respiratory Syndrome Coronavirus in a Healthcare Worker. Manal Al-Gethamy, Victor M. Corman, Raheela Hussain, Jaffar A. Al-Tawfiq, Christian Drosten and Ziad A. Memish.
   http://cid.oxfordjournals.org/content/early/2015/01/01/cid.ciu1135.long

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MERS-CoV snapdate...

MERS-CoV detections by month and year

As can be seen from the graph below, the peaks of MERS-CoV detection have been driven by humans and their infection prevention and control issues - but what maintains the virus in between those lapses? 

It seems clear that MERS-CoV is entrenched among camels in the Middle East and Africa but how is it getting to humans, and how is it dong that in such small numbers over such a wide area? These have been questions for 148 weeks. 

It's a good thing this infection transmits so poorly between humans.

Click on image to enlarge.

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Case->outbreak->epidemic->publication->learn a lesson...repeat

The global cumulative curve of suspect+probable+confirmed
cases EVD cases (orange) , suspect+probable+confirmed
EVD deaths (red) and the confirmed cases (yellow dots)
Updated from last WHO data posted 10JAN2015 AEST.
Click on image to enlarge.

When looking at the PubMed database search results for 'ebola', one can have no doubt that something big must have happened lately to drive such a massive number of science doers and writers to their keyboards. 

And of course something did - the world's largest, most widespread, multinational and longest running epidemic of Ebola virus disease (EVD) which roared through Guinea, Sierra Leone and Liberia. At the end of 2014 there were 20,000 cases and 8,000 fatalities - and those were just the cases we have seen added to official lists and made public.

A tally downloaded from the PubMed search engine
based on numbers returned using the search term 'ebola'.
Click on graph to enlarge.

The adjacent image shows what the US National Library of Medicine's search engine generates when one searches for 'ebola'. The search engine, called PubMed because it makes the MEDLINE database public (MEDLINE being the Medical Literature Analysis and Retrieval System Online, or MEDLARS Online), lists many of the world's life science and biomedical publications that meet the PubMed standards; currently >24,000,000 citations. In 2014, a lot was written about EVD.

While a lot of the 'ebola' publications in 2014 were commentaries and a lot of reviews that mostly presented the same information, these were necessary to feed many different groups of readers and specialities hungering for background on EVD and the ebolaviruses and how these related to them and their roles, patients and lives. 

I had cause to scan the literature on a daily basis for a few weeks and was particularly impressed with the New England Journal of Medicine's clinical papers and the BMJ's summaries and updates. Of course Science/Sciencexpress and Nature had some beautifully informative articles as well - delving into the humanity behind the numbers and seeking answers to questions we were all asking. I thought PLOS Current Outbreaks (although I'll never enjoy reading that layout), Lancet, Lancet Infectious Diseases and Morbidity and Mortality Weekly Report also stood out in 2014. 

Some of these articles came out very quickly and many were available without the need to breach a paywall. But some of the research...I can't help but wonder how many lives could have been saved if studies detailing and reinforcing the apparent benefits to survival from the aggressive use of intravenous fluids and electrolytes could have come out sooner-through whatever venue. What if we'd talked about, researched or actually published better personal protective gear designs earlier? Imagine if the world had registered that Ebola virus seemed to be in the region years ago, when research papers suggested it. Would any of this knowledge have saved more lives? Who knows? Would the focus on what needed to be delivered to West Africa have changed because of earlier dissemination of need? Would more point of care chemistry instruments have been prioritised? Would the urgency about the need for more healthcare workers have been stepped up if more specific examples of why they were needed were out there for our leaders to be briefed on? Probably unanswerable questions.

Why can't humans ever seem to learn enough to prevent the event sneaking up and whacking us senseless? Why is it always after the event that the light dawns and processes are created for 'next time'?

There will be many more publications to come in 2015, spinning out of this epidemic and the events yet to unravel. Hopefully they will create enough memory for the world to be better prepared for next time. Prepared for a little...uooh - goober fish...

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H7N9 outbreak #3 underway?

What better way to start 2015 than a snapdate!! For those who are new to them here on VDU, they were initiated here and defined here as snap updates - posts that don't have lots of detail and chat...although they almost always end up having lots of chat!

Figure 1. H7N9 cases by week of onset (or hospitalisation
or reporting dates of the preferred onset date was
not made public).
Click on image to enlarge.

This one is an update of the situation of one of the many avian influenza viruses ("bird flus" if you must) around again - avian influenza A(H7N9) virus, or just 'H7N9'.

In Figure 1, I've taken the huge liberty of adding in the start and end dates of the 3 outbreaks of H7N9 to date; and in doing so, I've said that China is in the early stages of one right now. I may well be wrong of course - this is a blog and these are my opinions - but it looks that way to me. 

Figure 2. China's northern laboratory network influenza
surveillance data up to Week 51 of 2014. [1].
Click on image to enlarge.

The case numbers for H7N9 in Figure 1 have been above zero for a little while and in particular November looked like a busy month (see weekly and monthly tallies here). Keep in mind that there is also a reporting lag - the time between date of onset (obtained from more detailed World Health Organization data) and the date the case was publicly reported (I rely on FluTrackers line list for these details). That delay can be a month or more on occasion; up to 38-days in late December. I suspect this is because China reports cases to the WHO in batches, something instigated toward the end of the 1st and 2nd outbreaks. So I suspect we will see more cases assigned to December, during reports that come out in January.

But it look like 'tis the season for influenza in humans in China (see figure 2 and the Chinese National Influenza Centre [2]) - and as some of us have discussed on Twitter, this is most probably due to the changes in weather (environmental conditions) which result in sustained viral survival on cough and sneeze-contaminated surfaces and in wet and dry propelled droplets and droplet nuclei; in both man and bird (see Hong Kong avian influenza detection report dates [3]). 

That sustained survival may well be all it takes for more of us to pick up an infectious viral dose.

Once the seasonal influenza viruses get a foothold in us, they spread well, causing disease in those who are susceptible and probably a bunch of unnoticed infections in those with previous exposure to that strain plus a healthy immune memory of that intrusion. By "seasonal influenza virus, I mean those that replicate in and circulate efficiently among humans, as opposed to the relatively inefficient avian subtypes.

So stay tuned to H7N9; it's not yet very good at spreading between humans but its established in birds and has been spilling over into humans since at least the beginning of 2013. We know how influenza can deal us a rough hand if the stars and its genetic segments align favourably (for it). Oh, and the continued reliance on fresh chicken obtained from and killed at live poultry markets. The majority of cases have very clearly had contact with poultry as defined by the WHO. 

References...

1. http://www.cnic.org.cn/eng/show.php?contentid=738
2. http://www.cnic.org.cn/eng/surveillance.php
3. http://www.chp.gov.hk/files/pdf/global_statistics_avian_influenza_e.pdf

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Influenza A (H5N6) virus in humans...

Provinces hosting human cases of H5N6
Adapted from [8]
Click on image to enlarge.

After late December's announcement of a human infection with another avian influenza subtype, H5N6. The tally of human infections by this subtype of FluA stands at 2 - that are reported anyway.

The ever vigilant @FluTrackers (and their line lists, news posts and commentary) and the always alert @Fla_Medic (and his Avian Flu Diary blog) have these cases well covered.

I just wanted to make a summary here for my own reference in making some slides for a talk next month.

1. ~23-April-2014. [1,4,5] 49-year old male (49M) from Nanchong City, Sichuan Province.
   Acute severe pneumonia, died 5-May-2014
   Exposed to dead poultry
2. 3-December 2014. [2] 58M from Guangzhou City in Guangdong province.
   Critical condition in hospital since 9-Dec-2014
   Exposed to live poultry but not ill contacts [3]

There have also been plenty of lethal animal infections by this and other highly pathogenic avian influenza (HPAI; referring specifically to the bird's outcome) subtypes and strains [7], including:

From an OIE Report 21-Oct-2014. [6]

1. 12,000 quails in Quang Nai Province, Vietnam in 18-Dec-2014
   http://en.vietnamplus.vn/Home/Quang-Ngai-destroys-12000-AH5N6-infected-quails/201412/59394.vnplus
2. 1,338 birds on a farm in Nanbu, Nanchoing City, Sichuan Province, China
   http://www.oie.int/wahis_2/public%5C..%5Ctemp%5Creports/en_fup_0000015698_20140731_162951.pdf
3. 20,550 (17,790 fatal) birds on a farm in Shuangcheng District, Heilongjiang Province, China, 23-Aug-2014
   http://www.oie.int/wahis_2/public%5C..%5Ctemp%5Creports/en_fup_0000016060_20141024_193420.pdf
4. Birds in Muang Nan and Muang Xayabouly Districts, Luang Prabang and Xayabouly Provinces, Laos in 12:14-Mar-2014
   http://wwwnc.cdc.gov/eid/article/21/3/14-1488_article#r4

No sign of anything like sustained human-to-human transmission of this viral subtype to date. But another for the influenza virus Rubik's cube.

References..

1. https://flutrackers.com/forum/forum/china-h5n1-h5n8-h5n6-h5n3-h5n2-h10n8-outbreak-tracking/164419-china-man-49-with-acute-severe-pneumonia-died-from-h5n6-nanchong-city-nanbu-county-sichuan-province?t=222782
2. http://www.who.int/csr/don/28-december-2014-avian-influenza/en/
3. http://news.xinhuanet.com/english/china/2014-12/23/c_133874590.htm
4. http://afludiary.blogspot.com.au/2014/05/sichuan-china-1st-known-human-infection.html
5. http://www.promedmail.org/direct.php?id=2451125
6. http://www.oie.int/wahis_2/public%5C..%5Ctemp%5Creports/en_fup_0000016060_20141024_193420.pdf
7. UPDATE ON HIGHLY PATHOGENIC AVIAN INFLUENZA IN ANIMALS (TYPE H5 and H7) from the Office International des Epizooties (OIE), otherwise known as the World Organisation for Animal Health
   http://www.oie.int/animal-health-in-the-world/update-on-avian-influenza/2014/
8. http://en.wikipedia.org/wiki/File:China_administrative_claimed_included.svg#filelinks

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Bats in a tree...

Meliandou and the burnt tree that
once housed a bat colony (from Fig 3, [1]).

While not snakes on a plane, I'm fairly sure the level of swearing has at times been at least as bad among those suffering from and dealing with the possible fall-out from these bats - if in fact they were the source for the biggest Ebola virus disease (EVD) epidemic on record.

A recent animal counting, trapping and testing study in Guinea included sampling in and around the village of Meliandou.[1] This village is, to the best of our knowledge, the site of the first animal-to-human, or zoonotic, transmission of the Ebola virus variant called Makona.[2]

The study team, made up of researchers affiliated with Germany, Sweden, Core d'Ivoire and Canada, did not find any decline in numbers of usually susceptible larger mammals around the index village; a sign during other outbreaks, of active local ebolavirus "activity". The team also found that primate hunting was not a big thing in this region, which is rather devoid of these and other Ebola virus mammalian host animals (including few of the Duiker, or forest antelope). Fruit bat hunting was common though.

The team captured 169 bats representing at least 13 different species and 6 families. But in the house of the 2-year old boy considered the epidemic's index case, fruits bats were not eaten and no bat hunters resided there. No Ebola virus RNA was detected in any bats and antibody screening results from bat blood were inconclusive. 

These findings led the authors to study Meliandou, resulting in an hypothesis that a nearby hollow tree that once housed a large colony of free-tailed bats [locally described as lolibelo - small and smelly bats - otherwise known to belong to the species of insectivorous bat, Mops condylurus of the family Molossidea; [3], may have been the source of  infection. Why only one child was infected this way when the tree was a site of frequent play by many children is not known. The tree was burned out in March 2014 which caused many bat deaths, some of which were collected for consumption. Sequencing of a PCR-amplified mitochondrial DNA segment found that in 5 of 11 ash and soil samples from around the tree, contained traces of Mops condylurus genetic material. So that species was at least there.

So, this is all quite far from a conclusive link between the 2-year old boy and these bats. But it does read as though every avenue has been tested in this village, perhaps apart from better animal antibody testing (serology), and some serology on the blood of those villagers who remain alive in Meliandou. 

Serology testing is going to be very important for answering many questions around EVD and this outbreak and epidemic. 

Of course this will raise the usual question of whether we cull all bats to prevent this from ever happening again. Don't be ignorant! Bats have very important roles in pollinating and thus in keeping our ecosystem going. Should we kill all bees because they sting us? I'm pretty sure I've been stung by a bee more times than I've had Ebola/Hendra/SARS/Nipah/MERS/Lyssavirus or any other bat-hosted virus infection. Killing off everything to prevent a very rare zoonotic event when better knowledge can resolve the problem is just a typically short-sighted and knee-jerk human reaction (not a fan-can you guess?).

One question that does still remain, and one that is of extreme interest to me, is how often mild disease results from an Ebola virus infection? Good, robust serology methods to the rescue.


References...

1. Investigating the zoonotic origin of the West African Ebola epidemic. EMBO Molecular Medicine(2014). http://embomolmed.embopress.org/content/embomm/early/2014/12/29/emmm.201404792.full.pdf
2. Nomenclature- and Database-Compatible Names for the Two Ebola Virus Variants that Emerged in Guinea and the Democratic Republic of the Congo in 2014. Viruses 2014, 6(11), 4760-4799.
   http://www.mdpi.com/1999-4915/6/11/4760
3. Mops condylurus via the IUCN Red List of threatened species (listed as of least concern)
   http://www.iucnredlist.org/details/full/13838/0

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