Most MERS may not have met a camel, but index cases may have

Donald G McNeil Jr., writing in the New York Times  a few days ago, posited the idea that camel contact, while not at all widespread among the majority of Middle East respiratory syndrome (MERS) cases, may play a role in the first cases that sparked clusters of infection; the so-called index cases.

These sorts of patterns, whether for camels, bats, baboons or cats, are key to understanding infection acquisition. 

We all look forward to reading more detailed local analyses of the sleuthing that seeks to define first contact with our MERS-CoV adversary...sometime in the future. 

Infection Scene Investigation (ISI): Kingdom of Saudi Arabia?

First noticed on Twitter from @crof.

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A stroll down Polymerase Chain Reaction lane

Dr Kary Mullis, 1993 Nobel prize winner and the co-creator of the Polymerase Chain Reaction (PCR; I have aliottle on PCR over at PCR Down Under), walks down memory lane describing the process of those very early discoveries while working at Cetus Corporation.

You can check out the whole seminar here.

Some key points were:

• PCR gets 41 million hits today
• Created PCR in the Spring of 1983 as away of increasing the demand for oligonucleotides ("oligos")
• Ron Cook developed the first automated oligonucleotide synthesizer machine that could create oligonucleotides in hours instead of weeks
• Before PCR, the only way to examine a specific bit of human DNA was to clone it and such genetic modification of bacteria was a cause of concern in the early days
• Speeding up the process of identifying genetic mutations was a driving factor behind the development of PCR
• The target produced by exponential amplification resulting from binding and extension of two oligonucleotide "primers" binding to a template, would overwhelm any non-specific product
• The original manuscript was knocked back by Nature and Science and ended up in Methods in Enzymology, after other's by Saiki et al, Saiki et al, and another by Saiki et al, a Symposium by Mullis also Saiki from Cetus were published. Lesson here for us all - write faster!

The Mullis story is an colourful one - as you can get a taste of from Wikipedia, his personal website, Cracked, virusmyth (describing his prior comments on HIV), this excerpt from Making PCR: A Story of Biotechnology and his book Dancing naked in the mind field.

Thanks to John F Mackay (no relation except by All Black) of DNature, an Antipodean PCR historian (nerd), for pointing out the presentation and for discussion.

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Middle East respiratory syndrome coronavirus cases amongst healthcare workers [UPDATED]

Click on image to enlarge. (a) the proportion of
MERS-CoV positives HCWs who have died (red) vs.
survived (blue), (b) the proportion of fatal cases (PFC; red) 
of MERS-CoV worldwide vs. the proportion of 
surviving cases (PSC; blue) (c) breakdown HCWs
as a proportion of all MERS-CoV cases (blue), HCW deaths 
as a proportion of all MERS cases (green) and HCW deaths
as a proportion of all MERS-CoV deaths.

With a lot of help from FluTrackers, the 2 of us have synced our lists to account for all the healthcare workers (HCWs) for which public data are available, that have been confirmed as MERS-CoV positive.

Some charts then.

We can see that HCWs make up approximately a sixth (18.2%; n=24) of all MERS-CoV cases.

Fatal infections in HCWs account for 2.3% (3/132) of all MERS-CoV cases (including living and deceased cases) and 5.4% of all MERS-CoV deaths worldwide are among HCWs (3/56). This last figure indicates that HCWs are at a relatively reduced risk of death from MERS-CoV infection when compared to other groups that have been infected.

For example:
NB: I have death data for 56 cases; age data for 125/132 cases; sex data for 120/132 cases); 27 comorbidities listed [underestimate]

• 63% of MERS-CoV deaths have occurred among those older than 55-years (50% of deaths among those >60-years; 38% among those >65-years; 59% among those <65-years)
• 46% of MERS-CoV deaths have occurred among males older than 55-years (38% among those>69-years; 30% among those >65-years; 45% among those <65-years)
• 82% of deaths )n=46) and 83% of cases have occurred in the Kingdom of Saudi Arabia
• 48% of MERS-CoV deaths occurred among those with comorbidities [this is an underestimate]So in the lower proportion of deaths represented by HCWs, while horrible in any proportion, may provide evidence to support that MERS-CoV is still not transmitting well, even in close quarters.

It may also mean that attending HCWs are adhering to good infection control and prevention practices. But it coudl just mean that we do not have data on all HCW infections/death and there are greater numbers of cases.

Finally, and perhaps most importantly, we should remember that HCWs may have some degree of resistance to disease caused by some viruses because of their constant exposure to patients with all manner of airway infections.

If HCWs may not show the same proportion of illness, but still become infected, they can act to spread cases among their contacts - patients and visitors. This was evident in the severe acute respiratory syndrome (SARS) outbreak where HCWs accounted for a fifth of all confirmed cases.¹

In other words, even a few cases in HCWs could have major implications for nosocomial outbreaks. If an emerging virus, such as the MERS-CoV, is being frequently detected in association with healthcare settings, that scenario may already be happening.

Some literature..

• Severe acute respiratory syndrome (SARS) and healthcare workers.
• Lack of SARS Transmission among Healthcare Workers, United States
• SARS in Healthcare Facilities, Toronto and Taiwan

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Why we don't need to do Gain of Function (GOF) influenza transmissibility studies

Professor of epidemiology, Dr Mark Lipsitch, Harvard School of Public Health, presented his views last week at the conference, Options for Control of Influenza VIII. 

His talk, entitled Transmissibility GOF Experiments with HPAI: Interesting Science but not worth the risk of an accidental pandemic, noted that these experiments will not (yet) produce results that are balanced by the risk of an accidental pandemic. An accident that is not beyond the realms of reality since such accidents have happened (FMDV in 2007, SARS in 2004 and possibly H1N1 in 1977) in high level biosecurity laboratories (BSL3/PC3). The required standards for these labs differ from country to country.

Further, Lipsitch noted, we don't need GOF studies for vaccine design when currently effective vaccines target haemagglutinin (HA) and not other influenza segments. Further our influenza surveillance is poor and our primary animal model for use in GOF studies for high-pathogenicity influenza virus, ferrets does not always "perform" as we expect it to.

So Lipsitch summarizes, there is much work still to be done to nail down influenza virus variability, impact of host genetic variation and whether before considering more GOF work. Any real benefit to offset the risk of GOF studies may simply be over-stated.

I enjoyed presentation this very much and it has greatly informed my understanding of the argument. Dr Lipsitch's views are clearly thought out and presented in a logical order intended to address some statements/justifications from the proponents of GOF influenza transmission studies.

Thanks to Avian Flu Diary for posting on this earlier.

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Today's MERS tetrad is....

Click on image to enlarge.

Another 4 confirmed MERS-CoV cases and the chart for KSA is exponential. On the plus side, many recent cases have been asymptotic  or symptomatic but mild or stable, which is a change in the recent trend of fatal cases. Of the last 26 cases, 7 have been fatal, and that proportion of 26.9% is well below the overall average, among the 132 global cases, which currently sits at 43%.

Today's case details (not yet on the English MOH site) with FluTracker's case numbering included (as it will be in all my posts from now on) are mostly female (yesterdays seemed to be all male), all in stable condition and they seem to be Riyadh-centric:

1. FT129: 51-year old female (51F), symptomatic female, contact of a mystery case, Riyadh
2. FT130: 47F, symptomatic healthcare worker (HCW), Riyadh
3. FT131: 39F, symptomatic HCW, Riyadh 
4. FT132: 38M, symptomatic HCW, Riyadh

The average age for cases is now sitting at 50-years and the median ages are 39 and 56. 

For fatal cases the average age is 59 and the mode sits at 56.

These represent a reduction in age reflecting the relatively younger cases of late. The younger, predominantly contact-based cases seem to have fewer underlying conditions as a rule - or at least we're hearing of fewer.

So, generalising, severe MERS continues to be an outcome among the older group with comorbidities and less so among contacts and the younger age band.

So, as I like to waste my time asking, I wonder what would happen if prospective testing were to be conducted on a sample of the general population, say in Riyadh, Medinah and Hafr Al Batin, without regard for symptoms? Ideally also in a "control" city from which no cases have been reported. 

My hypothesis is that the average age of MERS cases would drop further and the PFC along with it. In other words there would be more asymptomatic and mild cases detected than we see now. That would really serve the needs of pilgrims and the Kingdom of Saudi Arabia. Maybe such studies are happening right now - who'd know?

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Happy Birthday rhinoviruses (RVs) - 60 years old today!

Predicted capsid model of HRV-QPM (Q=Queensland;
PM-initials of the then PhD student who did all the work).
This distinct virus is now known as HRV-C3.
It was the first HRV-C type to be sequenced,
clinically, epidemiologically and virologically
characterised and modelled. It was the third HRV-C
polyprotein sequence to be placed on  GenBank.

On September 12th 1953, the Common Cold Unit (CCU, Salisbury, United Kingdom) reported isolating the agent of the common cold in laboratory cultures. The article was authored by Dr (later Sir)Christopher Andrewes and colleagues in The Lancet.

The isolate, called D.C. after Dr Donna M. Chaproniere's donated cold sample, was only able to be grown while the lung tissue from a particular embryo remained. Once stock was exhausted, the viral culture failed. The D.C. type was not able to be characterized until 1968, by which time another variant of that type had already be given a name; RV-9.

More reliable, repeatable RV culture were achieved in 1956 Price et al (the JH type) and 1957 by Pelon et al (the 2060 type). Back at the CCU, it was found that increasing the acidity, lowering temperatures and rotating the cultures increased the success of virus isolation. The use of increased acidity was discovered by accident when CCU's Dr David Tyrrell had to replace some medium that was killing his cultures. He borrowed (as we do) others' stocks to tide him over. During this process he noted a sign of viral replication  his cultures were being killed  He eventually deduced it was because of the acidity of the new medium compared to his previous work.

 21,915 days later there have been a number of interesting developments to come from the study of RVs:

• A type is the name for a distinct RV; that type found in another patient anywhere around the world is called a variant of the type. Specific criteria now exist to define types and variants, and to identify a new HRV type.
• Recently, HRVs became RVs - the host bit was dropped but their individual names remain "HRV" and they now have the species name included e.g. HRV-A1
• There are >150 distinct RV types
• As many as 70 RV types can circulate at a single site at one study period
• The early RVs were initially classified as echoviruses (ECHO-28; later RV-1) and have also been called ERC viruses, muriviruses, Salisbury strains, coryzaviruses and enterovirus-like viruses
• RV-Cs do not grow using any routinely used cell culture lines, but can be grown in primary tissues and differentiated multilayer cell cultures at the air-liquid interface
• RVs are the most frequent virus to be detected in children and adults with acute upper respiratory tract infections including the "common cold"
• RV infection of adult chronic obstructive pulmonary disease ( COPD) patients may precipate outgrowth of Haemophilus influenzae, not seen among healthy RV infectees
• RVs are also associated with fever and influenza-like illness (ILI), where and they can be near impossible to discriminate from some ILIs without laboratory testing
• RVs are the viruses most frequently detected in wheezing exacerbations ("attacks") in those with asthma where they, more than any other virus, seem to take advantage of antiviral immune deficiencies. While RV-Cs appear to be more exacerbatory, I personally believe this is just an artefact of small, short studies
• RVs are found more often than other viruses in people without overt signs of respiratory disease; but as a proportion of all viruses, RVs are less often found in well people compared to most other respiratory viruses. 
• RVs do not persist (a given RV type is not detected beyond 2-4 weeks) except in those with serious immune deficiency such as those undergoing lung transplant
• There used to be a genus Rhinovirus, but that was abolished and now the three RV species (A, B, C) sit under the genus Enterovirus
• There is no vaccine or broadly available antiviral for HRVs although both are being actively researched now.
• Prior to the use of PCR to detect RVs in 1988/1989, epidemiology studies looking at the impact of a specific respiratory could not account for 50+ HRV-Cs (and perhaps some fastidious HRV-As and Bs)
• RV-Bs are considered "wimps" by those in the know and they are always under-represented when found i.e they appear to circulate in smaller numbers than chance would dictate they should

So, many happy returns little guys. Long may you educate our immune systems with your constant challenges, long may you interfere with the seasons of other viruses and long may you make me write silly titles for reviews when under your mind-altering influence (that's my excuse anyway). 

Much may have been written about other respiratory viruses over the years, but the HRVs are always with us, always challenging us and always causing problems for us. To study RVs is to study all respiratory viruses and diseases of the upper and lower respiratory tract. To exclude them from study or test is to fail to understand these diseases.

Some literature...

1. Hilding,A. The Common Cold. Arch Otolaryngol. Head Neck Surg. 12, 133-150 (1930). 
2. Tyrrell,D.A.J. & Fielder,M. Cold wars: The fight against the common cold (Oxford University Press, New York, 2002).
3. Propagation of common-cold virus in tissue cultures.
4. Outgrowth of the Bacterial Airway Microbiome following Rhinovirus Exacerbation of Chronic Obstructive Pulmonary Disease
5. Newly identified respiratory viruses in children with asthma exacerbation not requiring admission to hospital.
6. Newly identified human rhinoviruses: molecular methods heat up the cold viruses.
7. Human rhinoviruses: coming in from the cold.
8. Do rhinoviruses reduce the probability of viral co-detection during acute respiratory tract infections?
9. Molecular characterization and distinguishing features of a novel human rhinovirus (HRV) C, HRVC-QCE, detected in children with fever, cough and wheeze during 2003.
10. Prior evidence of putative novel rhinovirus species, Australia.
11. Human rhinoviruses: the cold wars resume.
12. Distinguishing molecular features and clinical characteristics of a putative new rhinovirus species, human rhinovirus C (HRV C).
13. Frequent detection of human rhinoviruses, paramyxoviruses, coronaviruses, and bocavirus during acute respiratory tract infections.

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MERS mounts up...

In a strange coincidence of numerals, the 4th Middle East respiratory syndrome coronavirus (MERS-CoV) report in a row from the Ministry of Health (MOH) of the Kingdom of Saudi Arabia (KSA) contains very little on 4 cases. 

I use below, the FluTracker's (FT) case numbering scheme because frankly, they produce the only numbering schemes for tracking cases of new or returning infectious disease that are systematic, reliable and worthy of our trust. 

It should form the basis for a worldwide numbering system for infectious disease outbreaks because it is also freely and publicly available such that any potential manuscript author can easily check it before submitting a research paper and then we could all know which case is being discussed. And by "we" I mean fellow researchers, not just interested parties. 

The KSA MOH could consider running their own table of data akin to that of FluTrackers, but augmented and using an adapted version of Crawford Kilian's wishlist to the MOH. Each (deidentified) case entry should include the following headings along the top row, filled out if and as they become relevant:

1. A unique, continuous identifying code specific to this emerging virus
2. Sex
3. Age
4. Occupation
5. Co-morbidities
6. Date of illness onset
7. Town of illness onset
8. Town of acquisition
9. Date of hospitalisation
10. Type of laboratory testing
11. Date of laboratory confirmation
12. Date of death
13. Date of release from hospital
14. Treatments/management
15. Town of treatment
16. Relationships to any other cases

Today's MERS-CoV cases are mostly asymptomatic. These cases are announced amid rumours of larger case numbers being tested, panic in hospitals over potential MERS cases, frustration from within KSA over the MOH's poor performance, and of the KSA cracking down on healthcare workers who pass on rumours as well as prosecuting bloggers.

Today we have:

1. FT#125: 22-year old asymptomatic male, citizen of Madinha (Medina), contact of another confirmed case (we shall call him Mr/Mrs/Ms/Dr X)
2. FT#126: 24-year old asymptomatic male healthcare worker in Madinha
3. FT#127: 60-year old asymptomatic male citizen of Riyadh, contact of another case (also unknown)
4. FT#128: 47-year old male citizen of Riyadh, contact of another unknown case, symptomatic but stable

This brings the tally to 128 with 57 deaths (proportion of fatal cases, PFC, at 45%). Where data for sex exists, males comprise 63% of cases and 74% of deaths in people confirmed as positive for MERS-CoV. 82% of cases come from the KSA and, if counting back to the retrospectively identified cases from Jordan, we take the first week of disease associated with MERS-CoV infection as that beginning 19-Mar-=2013, then we are in 78th week of MER. 

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FluTrackers: Updating the ordinary about the harmful.

FluTrackers are a rock onto which we bloggers hold for dear life while the torrents of poorly-crafted, or well-crafted but just plain overwhelmingly vast, information break over and around us each day.

It sometimes seems like FT posts before the events even happen. Possibly they do since they also track a lot of related detail and background information so they see trends that may precede the particular case or outbreak "offical" announcement  But they have very strong principles and they clearly discriminate between what is confirmed and what is under investigation  They want you to know what's going on when no-one else has yet got the message to you. 

I think the dedication that this driven band of multi-lingual fact-seekers displays is worthy of honorary doctorates. 

Perhaps they could be made founding members of  a Division, Infection Notification: Forum for Organised Real-time Monitoring - now that's a name by someone who really wanted the initials to spell out I.N.F.O.R.M.

Anyway, I wish the example set by FluTrackers was one that more public health entities followed. Information that is quickly and publicly available, all the time, on everything, from everywhere.

Cheers from VDU.

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MERS-CoV fatal cases by week

Click to enlarge. MERS-CoV deaths (red bars) each week against a
backdrop (green) of total cases surviving + fatal, globally.

As requested on Twitter overnight, this shows the confirmed weekly MERS-CoV-positive deaths across time.

Not updated for today's 4 new cases though.

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The case against over-interpreting MERS-CoV detection by month...

Click to enlarge. MERS-CoV cases plotted by month of
detection (global data; combining 2012 and
2013 confirmed detections).

There are a number of reasons why I started my post yesterday (my time) with "I'm the first one to say its way to early to be talking about the seasonal distribution". Let's look at some of those reasons today:

1. Where there are few positives in the chart, there has also been very little testing done. The first validated PCR assay was published in 27th September 2012. So Sept-Dec 2012 cases are few and far between for this reason.
2. We are not yet 12-months beyond the announcement of the discovery of MERS-CoV (then nCoV and subsequently HCoV-EMC/2012). It was announced via ProMED on the 20th of Sept and the first genome and clinical study went online 17th October 2012. So no real screening had been done before that time. Cases shown prior to Sept 2012 that identified were retrospectively and not the result of systematic screening
3. As far as I know, screening is still mostly done on a case by case (and contacts thereof) basis. We don't know whether MERS-CoV is circulating endemically in the KSA or any other peninsula country. This is an important data gap since it may be humans that are acting as the reservoir - for all we know
4.  If we look at my post prior to the seasonality chart last night, we can see that cases are climbing steadily - have been since April, and there is no real sign that there is a change in that climb by month. Some reduction of numbers July & August but September is shaping up to be a big month.
5. The spike in cases starting in April was related to a hospital outbreak (the Al-Hasa cluster). And things have rolled on since then. What triggered that outbreak or how the first case(s) acquired the infection remains unknown

So why draw the chart if it is not an accurate representation of true seasonality? Because it gives us an idea of how all the cases officially announced so far are falling out over time, based on the data we have. 

But it should not be over-interpreted. 

We'd need a much greater number of cases and probably a couple of years of surveillance (including community screening) before we could accurately define whether MERS-CoV appears with any seasonal recurrence. Nonetheless, the seasons, or events that happen with seasonal regularity, may influence the risk of exposure and spillover. Also, most of the other seasonal human CoVs occur at their peak every couple of years, and even then, some occur in very low proportions of specimens from people with acute respiratory tract infections. That may be irrelevant to an emerging CoV, or not, so it may take even longer before we can speculate on any seasonal regularity to MERS-CoV infections; if we don't first stamp out the virus altogether as we did with the human SARS-CoV.

So to conclude, before I have to find something and PCR it, given the small amount of data we have, and hints that it might be only the tip of that well referred to iceberg, the more we can extract from what we have the better our chances of finding some clues to the host and some risks for acquiring infection.

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Can MERS-CoV seasonality tell us anything about acquisition of MERS?

Click to enlarge. Combined MERS-CoV cases for 2012 & 2013.

I'm the first one to say its way to early to be talking about the seasonal distribution of a new or emerging virus when there are only 124 cases worldwide. 

Right. 

Having said that, I thought I'd plot the cases by date of illness onset or (less satisfactorily) date they were first reported (even if that first was the report of a death). 

When combining the 15-months worth of case data for 2012 and 2013, the graph revealed a single "season" or at least larger numbers around summer in the Kingdom of Saudi Arabia (KSA). Because >80% of cases have occurred in the KSA, I have also listed a few festivals (some of which are frequented by camels) as well as the peak temperature variations and dust storm activity.¹ 

While I have no idea whether weather could be kicking up clouds of infectious CoV, it is an interesting co-occurrence, as are the presence of a number of festivals before case numbers spike. The Saudi Gazette commented that the risk of [acquiring?] bacterial and viral infections increases during dust storm season as do complication due to allergen exposure.

Of course we also know that some large clusters of cases have originated form hospital outbreaks and so environmental factors may play very little role at all. Or they might. Its impossible to say. But it is worth considering what could be happening up 2-weeks prior to a sharp rise in cases - if only to identify 1 index case that then ended up triggering a hospital outbreak.

1. Dust Storms in the Middle East: Sources of Origin and Their Temporal Characteristics. http://ibe.sagepub.com/content/12/6/419.short
2. http://www.magazine.noaa.gov/stories/mag86.htm
3. http://www.saudiaramcoworld.com/issue/200803/heads.high.htm

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MERS-CoV cases continue to climb

Click to enlarge. Global MERS-CoV cases by week and
the accumulation of cases.

The latest chart of Middle East coronavirus case spikes by week combined with the accumulating tally of cases.

This paints a picture of unrelenting case growth. The curve took a sharp turn upwards in April and hasn't slowed since. This is in marked contacts to influenza A(H7N9) virus cases which were brought to a screeching halt in south east China earlier in the year.

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Combined interferon and ribavirin therapy an option for early MERS-CoV intervention?

Falzarano and colleagues write in Nature Medicine that the combination of ribavirin (an antiviral) and interferon-a2b (a cytokine key to our antiviral defenses) improved the health of MERS-CoV (EMC/2012) inoculated rhesus macaque monkeys. 

This builds on the March Study by Falzarano et al, which reported  the usefulness of this drug cocktail in reducing virus production in a cell culture system.

Treated infected animals did not suffer from increased respiratory rate, breathing difficulties or increased white blood cell counts (mostly due to neutrophils). Treated infected animals also showed no X-Ray changes in their lungs 1-day after infection and little change beyond that. Untreated animals showed mild to marked evidence of pneumonia and also lower levels of markers of inflammation and copies of viral RNA genome.

The macaques were inoculated with 10⁶ tissue culture infective doses (TCID₅₀) by combined intratracheal (lower respiratory tract), intranasal (upper respiratory tract), oral (ingestion) and ocular routes. That seems to represent a fairly "shock-and-awe" cocktail of inoculation routes compared to how humans may get exposed. Viral RNA was detected in spleen, kidney, lymph nodes, upper and lower respiratory tract and airways in the untreated animals - and many of those sites in the treated ones. The relevance of this study to MERS-CoV transmission is probably limited, but then it's not a transmission study, it's a treatment study. There is another article cited as in press from part of this group. It may further address tissue replication; Novel human betacoronavirus causes a transient lower respiratory tract infection in a rhesus macaque model. Proc. Natl. Acad. Sci. USA.

Interestingly, disease in the macaques is at best mild to moderate in severity, so how the drug cocktail would work when faced with severe human disease...which may take longer to develop...remains unclear. Also unclear, is what disease would look like in macaques with a similar degree of comorbidities to those seen in the most severe human MERS cases.

The main proviso is, the cocktail must be administered early; it was administered 8-hours after infecting the monkeys here. 

With a 5-working day to 2-week turnaround in testing for MERS-CoV, treatment would have to be started at first suspicion and even then might not meet this window. Given the Qatar GP story yesterday, that window would be long shut, painted over and boarded up.

Nonetheless, this is a very encouraging finding and a very nice piece of work that adds an important step in the path to providing a therapeutic option to MERS-CoV infections.

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A memo to the Saudi Minister of Health...

Crawford Kilian has written a memo to Abdullah Abdulaziz M. Al Rabeeah, MD, Minister of Health, Kingdom of Saudi Arabia.

It is brilliant. 

Please read the entire thing. I have an excerpt below, but it is only a fragment of the whole glorious piece.

Your government, Minister, is now risking a similar problem. Both medical experts and the media are growing impatient at the erratic flow of information on MERS, and I hear rumours that Saudi hospital staff are as alarmed as those in Canadian hospitals afflicted with SARS ten years ago. And well they might be, when this virus seems to thrive in healthcare settings.

An aggressive, open communication policy is now urgently called for. Rather than indulge in a litany of past problems, I would like to recommend some steps your ministry could take right now to ease concerns around the world while also ensuring solid support from Saudi professionals and public. 1. Frame a detailed, standard format for reporting each case. At a minimum, this should include:

1. Frame detailed, standard format for reporting each case. 
At a minimum, this should include:

• the age, gender, and occupation of the patient;
• mention of specific underlying medical conditions, if any;
• place and date of onset;
• a description of treatment and place of treatment;
• the specific relationship, if any, to previous cases;
• tests administered and results of those tests;
• if possible, a statement by a Ministry spokesperson putting this case in the context of recent events.

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Saudi Arabia takes the initiative on MERS research

A coronavirus virion schematic.
IanM, Virology Down Under.

In what many might describe as well overdue, an independent Saudi Arabian scientific organization, the King Abdulaziz City for Science and Technology (KACST), has called for grant proposals to conduct research on coronaviruses (CoVs). 

The Arab News reports that several areas of research will be considered, as well as CoVs.

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MERS cases jump by 8 today...biggest 24-hours in 15-months?

Distribution go cases by site of likely acquisition.
Based on publicly available data.

The Kingdom of Saudi Arabia's (KSA) individual list of Middle East respiratory syndrome coronavirus (MERS-CoV) cases that have been acquired within its borders (and that's just to the best of my knowledge) is at 101. It's just a number but its also 81.5% of all laboratory confirmed cases to date. And it rose to 124 by a jump of 8 cases today (VDU time that is).

The latest KSA cases continue to pop up in Hafr Al Batin (Batin) Medinah (Medina) and Riyadh. Contacts (~4/8), healthcare workers (~1/8) and comorbidities (~3/8) feature heavily - and that's just among the ones with those details included. We're missing sex on most and dates of onset have been getting more rare since May.

Within those 8 cases are 3 deaths (37.5% of those cases). Are these the first reports of these people? How long is the turnaround time for testing currently? This proportion is below the global proportion of fatal cases (PFC) which as of just now stands at 46% (57 deaths have have data available to use in this calculation)

The other thing we should factor in is co-infections with other respiratory viruses, and with bacteria. The viruses, as noted in my previous post, may now be starting to increase in prevalence as the "cooler" months affect the region. None of the broader testing data (presumably they were screened for other pathogens as well) are available on recent cases and few details available on earlier cases. 

Some things that are unknown on this topic:

1. How MERS-CoV interacts with other viruses - has any virus just finished up its seasonal peak? Something that may have interfered with MERS-CoV circulation at a population level?
2. Are we seeing more MERS-CoV cases now because of a change in environmental conditions? His could be anything from temperature to humidity to impact on animal movements to festivals to dust storms

8 cases in 1 day. I think the first time I have seen so many cases in a row on my list in a 24-hour period (not actually at 24-hours yet). Many questions start arising without answers.

Even with Prof Memish's 2nd personal update through ProMED yesterday, it feels like cases are starting to appear faster than the local health authorities in these regions can manage them. Or has something changed with the virus itself?

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Flu-like symptoms on the rise in Qatar...

The Gulf Times notes a rise in cases of "flu-like symptoms" in Doha, Qatar. Dr Sameer Kalanden, a general practitioner (GP) notes a rise on cases coming to the clinic. He usually prescribes medication  or "an injection" to reduce the fever (please don't let it be antibiotics..oh. It is antibiotics). 

If there is no sign of improvement, even after a 2nd visit, he refers the case to Hamad General Hospital (managed by Hamad Medical Corporation; HMC).

Another GP confirmed the recent rise in cases with symptoms of "flu and common cold" rising "these days". He also refers cases with more severe respiratory disease to HMC.

So from that we might be able to conclude:

1. HMC may be the testing lab for Middle East respiratory syndrome (MERS) coronvirus (CoV) in Qatar. We also know that may/all MERS-CoV cases are confirmed by UK collaborators
2. That only the most severe cases of illness will be tested for MERS-CoV
3. GPs do not refer any other acute respiratory illnesses for MERS-CoV testing routinely
4. There is considerable concern about MERS in Qatar - but not a lot of structure to resolve that concern

This sort of anecdotal report is a great way to bring attention to what isn't being done, but it would be much more helpful to know what is being done in Qatar, given its recent local cases and deaths. 

As I understand it, Qatar is entering it's cooler months. Looking through the literature, there are not a lot of papers on respiratory viruses from Qatar. In one paper by Wahab and colleagues in 2001 in the Journal of Tropical Pediatrics, we see that HMC testing defined the peak season for respiratory syncytial virus (RSV) in children as November-January in Qatar (data from 1996-1998 combined, included 257 previously healthy children). 59.9% of these cases were diagnosed with bronchiolitis, 17.6% with pneumonia and 35.8% had an infiltrate in their lungs. RSV cases start rising from September though. The authors note this seasonality is similar to other temperate countries in the Gulf region. And this is just 1 virus of 200.

In another study, this year, in Archives of Virology, Althani and colleagues (Qatar University and HMC) tested 200 adults with asthma or chronic obstructive pulmonary disease (COPD) across winter (October 2008 to March 2009). While virus detections were relatively few (18% of patients), most seasonal viruses were present during this period - more so in asthma than in COPD. These included rhinoviruses, HCoV-229E, NL63 and OC43, parainfluenza viruses 1-3, RSV, adenovirus, influenza B virus and human metapneumovirus.

So this rise in cases noted by the GPs above may be nothing more than the usual start to the respiratory virus season, made to look more scary because of the recent MERS-CoV outbreak. Or it may be more than that.

I believe its time to be seriously considering what local laboratory testing capacity exists on the ground in the Arabian peninsula.

If the hajj stirs up case numbers, as many suspect it will, having limited to no ability to quickly resolve a flood of potential cases will result in a management crisis. Cases will accrue quickly and "probable", rather than "confirmed" will become the word of the day while trying to prevent spread in hospital environments.

If it looks like a duck and quacks like a duck, it may be just a rhinovirus. 

Case numbers will also be added to, as they always are when surveillance is heightened for a new agent, because seasonal endemic human respiratory viruses are circulating as well and those infections cannot reliably be discriminated from mild to moderate MERS-CoV using patient observation alone. 

Currently, MERS-CoV results in the Kingdom of Saudi Arabia may take up to 2 weeks to turnaround (if you follow me on Twitter you will have seen this time frame suggested to me last night). 

If the cases seen by the GP today were MERS-CoV positive, they would 1st need to return with a continuing fever before being tested and then that result would be revealed either too late to reduce the risk of a transmission event, or perhaps too late to be of use in applying novel antiviral treatments on that patient.

Time is of the essence. And more testing is paramount.

Thanks to @makoto_au_japon and @dspalten for bringing this to my attention.

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Hafr Al Batin MERS-CoV cluster grows...

Click to enlarge. The red circle indicates Hafr Al Batin in the north east of the
Kingdom of Saudi Arabia.

Apart from Riyadh's latest flurry of cases, Hafr Al Batin (Batin) has been hosting cases in healthcare workers (HCWs) since July. Lately though, we've seen seeing more HCWs - with reports suggesting as many as 10 in the cluster, and the possibility - raised via numerous local media and other reports - of more in this cluster. As with most clusters, cases seem to include human-to-human transmission events.

Is this a hospital based outbreak, a change in the virus to something more transmissible  or some particular activity that is exposing people in this region to more animal host infections?

Those long-awaited MERS-CoV full genome sequences we heard about recently are still not here, but if they were, they likely won't include recent strains like the ones in Batin. We really need to get over his whole-genome fetish and get some subgenomic sequencing going to reduce turnaround time. 

There are already PCR primer sets published by Corman et al that could monitor some smaller genome (subgenomic) regions of MERS-CoV and this should be able to be done locally, perhaps in , gasp, a collaboration with local Universities  But this does not seem to be happening for some reason.

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