MERS-CoV detections and deaths: is the war on MERS making headway?

For a few days now its felt as though we are seeing a more deaths in each Kingdom of Saudi Arabia (KSA) Ministry of Health (MOH) report, than we had been for a while. All very precise language there.

Currently there are about 161 fatalities among the 571 MERS-CoV detection. According to those numbers, 28.2% of people testing positive for MERS-CoV have died.

NOTE: Specific dates for some deaths are missing; date of reporting has been used instead.
The chart use 151 of approximately 161 deaths.
Click on image to enlarge.

Earlier in April, when the case numbers exploded thanks to a healthcare-associated outbreak, I wondered on Twitter if we'd see deaths "catch-up" to announcements as cases struggling for life in hospital, eventually succumbed to the damage started by their MERS-CoV infection. This is a virus with an apparently determined ability to wreak havoc in the lungs and kidneys of those who often already have an associated underlying disease of these tissues, and/or the cardiovascular system.

From the chart above, it looks like that catch-up is happening as the number of fatal outcomes (red dots) among the total of laboratory-confirmed MERS-CoV detections (green mountain) has been rising from mid-April onward. 

Most notable to me is that the proportion of fatal cases (PFC) is now also rising as the number of new detections no longer outstrips the number of deaths being reported. 

This is the first rise (rise >1% in PFC at least) since the beginning of March and reverses a trend of relatively stable PFC which dated back to late Aug-2013. 

This bears watching both at face value but also in light of the recent concerns about extra testing and its impact on straining the KSA healthcare system. It might be more prudent to discuss the significant strain being placed on the KSA healthcare system by filled hospital beds and intensive care units and the supportive management of severely ill people detected as result of that testing. 

The testing  should be telling the MOH (even if it no longer tells us) in which hospitals the problems lie. At this stage, 21-days after the KSA Health Minster was replaced (21-April-2014), we'd expect to see the case numbers dropping as (hopefully) changes have been implemented that (hopefully) focused a stern gaze toward (hopefully) improving healthcare worker safety and (hopefully) infection prevention and control (IPC). 

21-days into the new Health Minister's watch lies well outside the upper limit of the known MERS-CoV incubation period. If changes were sufficiently sweeping and if the war on MERS was entering a phase, detection numbers should be dropping as steeply as H7N9 cases do after a wet market closure. But they are not. Not yet anyway. 

The accumulating MERS-CoV detections (green mountain) are looking to be slowing a little, which is good news. But of course with that slowing, I expect we'll see those red and back lines rise in the weeks ahead as deaths keep occurring. Which is not, and will not be reported as, good news. About the only thing to stop that numerical marker from rising would be a new outbreak of cases. Not something we want to see. And of course, it would only be a smoke-screen for the fact that MERS-CoV positive people are still dying from MERS-CoV infection and the complications that ensue.

Last point for this post. Recent KSA MOH reports are more up-to-date than they have been for a while so we can see that MERS-CoV infected people are still being admitted to hospital, even in recent days (e.g. 7-May), and MERS-CoV infected people are dying relatively recently too (e.g. 10-May).

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H7N9 deaths jump significantly....

Click on image to enlarge.

Twitter was buzzing this morning with news that several sources had announced a new total number of deaths in human cases of H7N9 infection.

It was not a total surprise that there were more deaths than we had heard about, and that is for several reasons:

• In Wave 1, Spring 2013 in South east China, there had been a greater proportion of deaths than we have seen in Wave 2. That's seemed unusual.
• After Wave 1, the proportion of fatal cases (PFC; see background here) sat up as high as 33%. Wave 2's high case numbers but few reported deaths had lowered that to 18% at one point. If the virus hadn't changed and human-to-human transmission had not changed then that was incongruous
• The media were reporting higher numbers than we had data for in early Feb and in late Jan, Xinua reported 26 deaths in Zhejiang alone for 2014 - this far outstripped any publicly data available

So now we see that the tally is 112 fatal H7N9 cases among people infected with a laboratory confirmed H7N9 virus, since the outbreak began in 2013; that tally includes both waves of human cases. That makes the PFC among the 361 confirmed human cases at 31%. 

So this one new piece of news has bumped up the PFC by 10%. From 1:5 (22% last week) to nearly 1:3 cases dying after acquiring infection. 

Thankfully, H7N9 is not spreading efficiently among humans (or chickens according to reports). But these are numbers to care about.

For comparison, my Excel sheet has 64 cases with data that I can cross-check (I believe that agrees with the FluTracker's count also). 

The last media update I looked at had a tally of 77 fatal outcomes. 

So we have between 35-48 people have died without any ability for anyone outside China to link them to:

• their age
• when they became ill
• where they were
• how they may have acquired their infection
• their sex
• time to hospitalization and diagnosis
• length of stay in hospital 
• what contacts they had and how they have fared. 

I think that this is a ball that has been not just been dropped, but buried in a hole and covered over with feathers. I'm disappointed by such a gaping data loss. And don't get me started about the absence of H7N9 sequences from 2014 cases!

Sources...

1. SCMP with higher death tallies than public data indicated
   http://www.scmp.com/news/china/article/1425289/january-worst-month-chinas-human-h7n9-outbreak
2. Xinhua lists 26 deaths in Zhejiang alone for 2014
   http://news.xinhuanet.com/english/china/2014-01/21/c_133060657.htm
3. VDU blog on missing deaths
   http://newsmedicalnet.blogspot.com.au/search?q=deaths+h7n9
4. Mike Coston's Aviann Flu Diary take one the new data, with other sources
   http://afludiary.blogspot.fr/2014/02/chinas-moh-h7n9-fatalities-higher-than.html?m=1&utm_source=dlvr.it&utm_medium=twitter
5. FluTracker's thread with links to eth WHO report
   http://www.flutrackers.com/forum/showthread.php?p=525996#post525996
6. China's Ministry of Agriculture report of enlarged H7N9 death tally
   http://translate.google.com/translate?u=http%3A%2F%2Fwww.moa.gov.cn%2Fgovpublic%2FSYJ%2F201402%2Ft20140220_3791429.htm&hl=en&langpair=auto|en&tbb=1&ie=UTF-8
7. The WHO report under the "vaccines" section
   http://www.who.int/influenza/vaccines/virus/recommendations/201402_recommendation.pdf?ua=1

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Tracking virus-related deaths using publicly available data...

Click on image to enlarge.

Here's the cumulative case chart overlaid with the cumulative deaths and PFC. see the story behind the term PFC here, created by VDU to avoid issues around case fatality rate/ratio (CFR) which relies on knowing when cases have recovered.

I have two PFC values charted here. In black dots, is my curated list based on fatal cases (n=40; red dots) that have been announced publicly. 

In yellow are the numbers gleaned from media releases and the WHO - the latest number being 52 fatal H7N9 outcomes. 

Somewhere towards the end of the initial H7N9 outbreak in May, we stopped seeing reports from China that could link fatal cases with those H7N9 cases they initially announced. If anyone knows of a complete public list of fatal H7N9 outcomes that contains all 52 cases with age/sex/date of illness onset/date of death/province, I would be most grateful to be made aware of it.

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H7N9: males and females among total and fatal lab-confirmed cases...

Click on image to enlarge.

Males are the predominant host for H7N9 cases that are severe enough to warrant a hospital visit (or the contacts thereof). 

As ever, we have no real idea of the extent to which H7N9 is circulating among those who are not ill enough to present to a hospital. Only the use of a sensitive virus detection method on less ill or healthy people could tell us that. Such testing seems to be anathema, perhaps due to cost (?), for H7N9, MERS-CoV or H5N1 for that matter. So much we don't know but settle for in the respiratory virus game. But some of us go collectively bananas when a case turns up somewhere "unexpected".

Finally, the H7N9 fatality data are severely hobbled by a lack of linkage between H7N9 case notification and which cases died. That linkage broke somewhere after April. Reporting has improved drastically of late with the WHO confirming cases and details but 12 fatal H7N9 cases are publicly lacking enough information to use in sex-related charts, age-related charts, dates-of-onset/reporting charts or dates-of-death charts. 

I'm grateful to the WHO today for responding to a request and noting that 52 deaths have been reported to them, bringing the proportion of fatal H7N9 cases to 29%.

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MERS-CoV and the host: a serious disease of those with disease

Case total currently stands at 150 including 64 deaths (PFC of 43%), with the World Health Organisation's latest update adding in the recent death (their tally says 149/63) and the Oman case and a new death being reported from eastern Saudi Arabia. The details for this latest patient are (FT#152):

• 56-year old male
• Comorbidities
• Contact of a previous case.

So, as the Oman case showed, transmission from a previous case can lead to mild illness. The Qatari case before that showed that a contact can be asymptomatic. This latest fatality highlights that under the right pre-existing disease conditions, even a 2nd "passage" of virus from a human to another human, can lead result in death. 

It's a very much about the health of the human host who acquires the virus, as we've seen all along with MERS and also among cases of influenza A(H7N9) virus infection.

The latest WHO update also notes that...

Patients diagnosed and reported to date have had respiratory disease as their primary illness. Diarrhoea is commonly reported among the patients and severe complications include renal failure and acute respiratory distress syndrome (ARDS) with shock. It is possible that severely immunocompromised patients can present with atypical signs and symptoms.

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Happy 1st birthday Middle East respiratory syndrome coronavirus (MERS-CoV)

A coronavirus schematic. The spiky bits give the virus
its name(corona=crown) and represent the
receptor binding, antigenic Spike protein. 

...I can remember when you were just a novel little thing.
How you have grown young prince and how clever of you to emerge in a Kingdom of all places (corona=crown, named for it's spikey appearance). You've certainly garnered attention worthy of a King given the relatively few cases of disease you gave been associated with in the first year we've known of you.

It was September 20th when Dr Zaki 1st alerted the world to the death of a Saudi man due to what looked to be a new coronavirus (CoV). Today we have over 135 cases 58 deaths (43%).

I've previously covered Zaki's disocvery and the problems posed for the Kingdom of Saudi Arabia (KSA) by the way in which he announced that discovery, apparently without the Ministry of Health's (MOH) foreknowledge. The way in which the sample was exported from the KSA without their prior consent was also problematic for them.
Soon after we heard of it, we had virus-detection assays with which we could seek out new cases. Were they used as they might have been in the days of the SARS-CoV? Nope. And there still seems to be only a single laboratory in KSA testing for MERS-CoV (despite reports of 3), with Dr Abdullah Al-Aeeri (a director of hospital infection control) claiming a 72-hour reporting turnaround time.

Is there an antibody detection assay that has been validated using a panel of known positive sera? Nope. There are some innovative antibody-detection methods around but why do they only include a single positive control? Is there no collaboration at all? Why is the KSA not leading the charge to develop these diagnostics and to hunt for an animal host? Why wait on advice from external organizations to screen samples? Why has the necessary testing capacity not been built well before now? Is it to do with that pesky material transfer agreement? I hope not because there is little evidence for that being a real block to anything from a public health standpoint.

At least we have some new MERS-CoV sequences to celebrate the birthday with. Although they and the 9 preceding them represent less than half of the relatively small number of cases described to date. Why can't the typing region sequences be released? That should really be part of the diagnostic process. Okay, those may not inform us about the evolution of key regions of the virus but they do confirm it is the strain we know. Why not focus on full or subgenomic Spike gene sequences? They might be a better sentinel for keeping tabs on MERS-CoV change over time.

Most of the detail about MERS-CoV and cases of MERS has come through the peer-reviewed scientific literature. That is pretty normal for respiratory viruses that are not notifiable. But it's generally a slow medium. Is MERS infection a notifiable disease? It is in some countries (e.g. the US and New Zealand), but is it at the epicenter of the outbreak, the KSA? I'm not sure. It's not obviously stated as such anywhere I looked on the KSA MOH website.

The World Health Organization politely notes:

WHO encourages all Member States to enhance their surveillance for severe acute respiratory infections (SARI) and to carefully review any unusual patterns of SARI or pneumonia cases. WHO urges Member States to notify or verify to WHO any probable or confirmed case of infection with MERS-CoV.

How's that been working out? In a nice summary of the lack of communication, Helen Branswell and Declan Butler highlight that, as usual, everyone  who was asked agreed that it's not working out well at all. In fact it's pretty woeful. And to add to matters, the latest WHO Disease Outbreak News (DON) takes the form of a summary of 18 "new" cases; no extra or confirmatory detail to be had from it. SO the KSA MOH is now the source for detail.

If we were talking about wanting more data on the monthly proportion of rhinovirus infections, the KSA would be justified in saying that the world doesn't need to know (I'd like to but that's my thing). 

If we were talking about influenza, then there are plenty of international public health sites publishing these notifiable data on the internet; here's Queensland, Australia's for example.

But we're talking about an emerging disease which kills half of the people it infects, is caused by a novel virus for which no host is known, which transmits between people in a way we don't yet understand, which is shed from ill (or well) people for an undefined period of time (if at all), which remains infectious in the environment for who knows how long, which jumps to other countries, which may only cause severe disease in those who are already ill with another disease, which may be endemically spreading within the community as mild or asymptomatic infections, for which there is no vaccine or proven antiviral therapy available..I'd say it's a no-brainer that at the very least the WHO deserves regular and detailed updates of what's going on. Reading between the lines, that does not seem to be happening even behind closed doors.

The mass gathering of pilgrims known as the Hajj is fast approaching. This may trigger a large increase in MERS cases or, in the worst case, a pandemic. I personally believe it won't go that far. We shouldn't forget is the 2nd Hajj for MERS. But perhaps the virus is much more widespread than it was in October 2012. But without testing data, we can only guess.

So, it's your 1st birthday MERS-CoV. But instead of wishing you a happy birthday you opportunistic, spiky little killer, I'm wishing Dr Zaki well and congratulating him on co-parenting the birth of this novel coronavirus. Going by what we've seen to date, his actions may have been the only way we would have ever heard of this virus otherwise.

And, as noted previously, but not given much air to in the above rant (thanks to @MicorbeLover for straightening me out)...

It's very sad that there are real people in these numbers who have died from MERS. You may have noticed that I try and stick with the cold number-crunching aspect of these outbreaks. It's not because I'm a heartless b&^$# but because that is not what this blog is about. That and my editorialisation and expositionary writing consume what little time I have spare. But I don't feel that I have enough information to make any other comments about these or any other lives lost to infectious disease. I personally feel that any unexpected and acute loss of life (if I had to scale loss of life) is the worst kind of loss; it's a waste of potential, a source of great sorrow for all involved and it's something we should all strive to prevent, if we can. I know that's not much to convey, but it's all I can offer from my kinda comfy chair in Brisbane. 

The MOH says it better in anyway; May Allah have mercy upon the deceased.

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