Middle East respiratory syndrome coronavirus (MERS-CoV): Age and Sex [UPDATED]

THIS PAGE IS NO LONGER UPDATED

This data visualization has been added to the single
MERS-CoV page now be found at..
http://newsmedicalnet.blogspot.com.au/2014/07/middle-east-respiratory-syndrome_17.html

A new static page on which I will update the MERS-CoV numbers as they relate to the age and sex of the people laboratory confirmed as infected.

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MERS-CoV detection and age...

Just a few different ways of looking at age of living and deceased MERS-CoV people, globally, since 2012.

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Jeddah changed the MERS-CoV age:sex landscape...

Note. Not every death or case is listed.
See bottom-left corner for breakdown.
Click on charts to enlarge.

I've broken down the age and sex in these charts.

As usual, it's mostly about males and older people until we get to the Jeddah outbreak.

In the top pair of charts (note the different scale used here compared to that used in the charts below) we see the breakdown for all MERS-CoV detections to date on the left and the fatal cases from among those on the right. 
An apple in terms of people shapes.

In the middle pair of charts we look at all cases form 2012 up until the day before the Jeddah outbreak. The total case pyramid shows an older age bulge but the deaths look very similar to those for all fatal outcomes. M:F is similar to the total case charts above.

In the bottom pair of charts we're looking at what happened from the beginning of the Jeddah outbreak until now. We see a marked change in distribution with many more younger adults being positive for MERS-CoV. We also see a major shift towards more females than we'd seen beforehand. All the result of more widespread testing and a greater healthcare worker contribution I presume. Strangely though, given the younger adult demographic here, we see no accompanying jump in numbers of children. Are they not subject to testing? Are the younger adults often foreign workers who do not have children/children with them with them? There is no reason for children to test any less frequently MERS-CoV-positive and they are also just as likely as healthy adults to get mild or asymptomatic disease (as far as we know). If positive, children will have an important potential role in the MERS-CoV transmission story, especially when visiting elderly relatives.

The recent Al Qunfudhah teacher who is MERS-CoV just reinforces that children are shaping up to be a strange data gap. Yeah. I know. Another one.

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Snapdate; MERS-CoV and the thickening age/sex pyramid..

Click on image to enlarge.

No, it's not the title for an epidemiologist's detective novel. It's a comparison of my previsou and my latest age/sex pyramids.

And it really looks like MERS needs to go on a diet. Its "waist" has broadened quite a bit as a sign of younger cases becoming part of the rogue's gallery of infected, if not afflicted, people. 

Also note the axis along the bottom has changed a lot between mid-April and now. So we have more total numbers but also more detections of virus in the under-50s age band.

And as always, males predominate in MERS-world.

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MERS-CoV by sex, week and age...

Two quick charts on the Middle East respiratory syndrome coronavirus (MERS-CoV; which I verbalize as "murrs coronavirus" just fyi )data.

The first chart shows a rise in the proportion of females (pinked dashed line; right-hand axis) during the Jeddah outbreak over recent weeks. But this does not change the fact that males still make up the majority of humans positive for MERS-CoV. For camels - I don't know sex, but juveniles seem to more often have RNA detected and less often have MERS-CoV antibodies present.

It's interesting that a similar rise in the proportion of positive females occurred in April-2013 when there was another healthcare-related outbreak around Al-Ahsa.

It would be nice to know what the sex breakdown is when comparing index cases to non-index cases. Does human-to-human spread involve more females as it goes along than does acquisition from camels - these presumably being a more common source for the sporadic cases that trigger each smaller cluster? Could a rise in the proportion of females be useful as a marker for an impending extended outbreak? Do men have most of the contact with camels? A few question marks there.

The sex distribution, by week, of MERS-CoV positive people and the proportion of those,
each week, who are female (shown using a 6-day moving average).
Click on image to enlarge.

The second chart plots the average age each week (an orange dot) and plots a 10-day moving average. The moving average continues to show the cyclical pattern I alluded to in my last post of this chart - whatever it means or doesn't mean. 

During the Jeddah outbreak, the average age appears to have dropped compared to prior to just the outbreak. But there is a lot of movement in the average age over time. Although, there does seem to be a downward trend after the Apr-2013 outbreak as well and another after something happened in October. Do we know of an outbreak in Oct-2013? Could this mark one that occurred but that we didn't hear about? Am I wearing my tinfoil hat again? So many questions.

Age drops among the tested population may be another marker of the wider or differently composed population that is being infected during human-to-human spread compared to when cases are sporadic and perhaps more closely camel-contact related. 

The average age, each week, of MERS-CoV positive people and a trend shown 
using a 6-day moving average.
Click on image to enlarge.

Or it may be nothing but noise from the incomplete data we have to play with here.

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H7N9 Snapdate: some quick charts...

Click on image to enlarge.

I don't have a lot of time tonight so this is just a quick post of some updated charts with a few summaries of some key features of the influenza A(H7N9) virus situation in south-eastern China. At writing it was at 432 detections with media reporting 128 deaths

Click on image to enlarge.

Guangdong is where H7N9 is still most active and it is this province that is the source of the continued cases trickling off Wave 2's peak.

Most H7N9 cases overall have been in Zhejiang and Guangdong provinces but lately, post-peak of Wave 2, there has been continued activity in Jiangsu province including a recent healthcare worker with no mention of "contact with poultry"; the absence of which stands out in World Health Organisation (WHO) reports because most cases are followed by affirmation of that phrase.

Click on image to enlarge.

In  the  survival chart above we see that most of the fatal cases, shown in red, are defined by an older age. Unfortunately, a lot more of the fatalities have been reported through the media without identifying details (48 of 128), than have come through official Chinese channels and out via the WHO. This lack of detail makes it impossible to clearly link a lot of the deaths to the case announcements. Only the custodians of these data know what this chart should really look like. NB: Since making the chart this morning I've found a handful more case details at FluTrackers, but public detail on fatal cases remains the weakest of any of the H7N9 data.

Click on image to enlarge.

We can see in the weekly chart on the right that the two H7N9 waves differed in timing, the width of their bases (more cases in Wave 2) as well as how "tight" their peaks were. Wave 2 has tailed off, but continues to spit out cases, while Wave 1 comprised both a steep climb and a steep decline in human cases.

Click on image to enlarge.

If we zoom in on Wave 2 we can see by looking at cases per day in the chart on the left, that between 0-4 illness onsets per day are being reported, as they have been since late Feb-2014. 

Is this the legacy of those regions whose live bird markets remained open or were only shut temporarily for disinfecting and restocking? Those regions with markets that were shut for much longer, or for good, do not seem to have contributed much to the continuing leak of H7N9 infections despite being key contributors during the peak periods before markets were closed.

Click on image to enlarge.

In zooming in on Wave 2's cases by week, but this time based on the region of likely acquisition of infection, we see that Guangdong province (brown line) has been the most consistent contributor of human H7N9 infections both late during the 2nd of the Wave 2 peaks, but also after the peak's decline almost everywhere else in south-east China. There was considerable publicised unwillingness from poultry producers to permanently close markets in this Province, a location with a major role in the nations poultry production. And so this little experiment incubates further and I have little doubt we will see the impact of that unwilingness late in 2014. 

Click on image to enlarge.

As noted above, public H7N9 death data do not allow good linkage with official case announcement data for about 48 fatalities, so my second-last chart tonight uses both public and media-release numbers to try and illustrate how the proportion of fatal cases (PFC) has changed across both Waves. The PFC seems to be holding fairly steady now between 17% and 30% (depending on source of numbers).

Click on image to enlarge.

And finally we see that the age and sex distribution across all cases (both Waves) is skewed to wards older males. Same as usual. If we look at this distribution (ran out of time to put in here) for the fatal cases, it is much more tightly grouped around the >60-year olds, but that females appear to dominate males in deaths during Wave 2, whereas it was the other way around for Wave 1.

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MERS-CoV case age over time...[UPDATED]

The top chart uses a 10-day moving 
average (Excel)  shown as a dashed orange 
line. Sub-charts A, B and C are data taken from 
the identically boxed sections in the top 
chart with a simple linear trendline added 
in (dashed orange line).
Click on image to enlarge.

The next in my quest to answer myself is a look at the average age of Middle East respiratory syndrome coronavirus (MERS-CoV) cases over time.

I've made a new chart (top) showing the average age (orange dots) of MERS-CoV cases for each week (Week 1 being that which begins 19-Mar-2012) from 2012 until now. 

A couple of things strike me about the top graph.

• There is a very small downward trend in the average age of MERS cases in 2014 (not shown but much more subtle slope than seen in the sub- charts, A, B and C) but nothing that screams "change in age of cases"! 
• There does, at least by eyeballing the chart, seem to be an occasional cyclical nature to the ages of MERS-CoV cases. There are at least a couple of these apparent cycles (boxed as B and C) in which there seems to be a high'ish average age in a particular week, followed by weeks of mostly declining age. What could be causing this - if it's not just an observational bias [or influence from the cases lacking age data; thx @dspalten]? My hypothesis for this pattern is that index cases in clusters are older (comorbidities and older males have been a hallmark of severe MERS cases) and that the people they infect, or that form part of any human-to-human transmission chain in some way, are younger (healthcare workers and family) so the average age drops as infection spreads. To look at this in more detail I selected 3 sub-groups of the data and re-charted them in separate graphs (A, B and C). A was chosen because it did not obviously look the same as B & C to me, but I wanted to check. The linear trend lines for B & C support an overall decline in age in these 2 "cycles", but not for A.
• In 2014 the pattern seems to have changed from one of cycles to what looks like a more consistent spread about an average age.
• The average age for MERS-CoV cases from 2012-today is 52-years. 
• It was 50-years, 12-Sept-2013 and 53-years, 26-July-2013.
• In 2013 the average of all cases was 51.9-years; in 2014 so far its 52.2-years.

Age pyramid of all confirmed MERS-CoV cases.
Click on image to enlarge.

There are a few ages missing for some of the recently announced batches of cases, so it will be interesting to see how they impact on 2014, if we see those details come out. 

Someone with much better statistical skills than mine should possibly test these data and see if there is anything to this. From a pattern like this we just may learn what to look for to uncover the source, the mode of acquisition or routes of MERS-CoV transmission among clusters.

Or not.

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Any differences in the sex of avian influenza A(H7N9) virus cases in different areas of China?

a) Male (blue) and female (lavender) lab-confirmed H7N9 human cases broken into the Province or Municipality of likely acquisition. b) The proportion of total H7N9 positives at each site of acquisition that are female (lavender).  The proportion of females in Wave 1 (Range of weeks beginning 18-Feb-13 to 20-May-12) and Wave 2 (07-Oct-13:current) are also shown as a horizontal line for comparison.
Click on chart to enlarge.

This new chart idea was just a look-see at whether there is anything out of the ordinary about the sex distribution of H7N9 human cases in the different areas of China. These are total numbers from both Waves of H7N9 season.

I've included case numbers in Part a) as well as proportion of females in part b) to show that a value of 100% must be place in context of only 1 POS!

Nothing much to see here folks.

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An update on avian influenza A(H7N9) virus cases in humans: Week 56

As we currently stand (this minute), there are 389 laboratory confirmed human cases of infection including perhaps 122 deaths (31% PFC). 

H7N9 cases are mostly noted in older males (Average age 54-years; Wave 1 57-years; Wave 2 53-years) with the major risk being exposure to birds and "poultry markets" (commas because it is not just poultry being sold at these markets). No sustained human-to-human transmission has been noted and no specific vaccine exists although one is coming soon apparently. Oseltamivir or zanamivir are useful antivirals while adamantanes are of no use because H7N9 is resistant. to them. The second wave has peaked but we are still seeing a shoulder off the main peak from Wave 2; smaller numbers of cases each week (no longer occurring every day), often from regions other than those with closed poultry markets or with only recently closed or temporarily closed markets.

First chart.
Click on chart to enlarge.

First chart: where is H7N9? It's in Southeast China, most cases having been acquired in Zhejiang province (139/389 cases; 36%) during both Waves of human infection and Guangdong province is currently a very close second place (95/389 cases; 24%).

Second chart.
Click on chart to enlarge.

Second chart: where has H7N9 been focused over time? We can see from this chart that Zhejiang and Guangdong provinces have accrued H7N9 cases most rapidly. While Zhejiang featured in both waves, Guangdong is of Wave 2. It will be interesting to see what happens if there is a Wave 3; without finding and controlling the source of human acquisitions and if the birds with the virus continue to have the virus, I expect we will see future waves.

Third chart.
Click on chart to enlarge.

Third chart: the waves of an outbreak. Wave 1 was 2013 while Wave 2 started in Oct-2013 but really kicked off in Jan-2014. Cases dived in Feb-2014 but there are still sporadic cases being reported each week. The Week (#53) beginning 17-Feb-2014 saw 8 cases followed by 7, 4 and 0 for subsequent weeks. Keeping in mind that there are around 4-12-days (currently averaging 8-days overall) between onset of illness and when a case get confirmed by a laboratory (or reported publicly if no specific lab date is available), we may see a few more cases assigned to the last week of February yet.

Fourth chart.
Click on chart to enlarge.

Fourth chart: Age and sex of H7N9 cases. The age pyramid shows a decidedly upside down pyramid indicating that H7N9 disease is one of the older age bands. It also shows that it is a disease of men morseo than women.

Fifth chart.
Click on chart to enlarge.

Fifth chart: age by week and proportion female. This is an interesting one. There was a dip in the proportion of female cases for the week the week beginning in 3-Feb (right hand y-axis) which bounced back up a week or two later. 

Sixth chart.
Click on chart to enlarge.

Sixth chart: H7N9 cases per day and the rolling average. The decline in Wave 2 cases continues with multiple recent days recently in which no new cases occurred.

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Looking at the age and sex difference between H7N9 Wave 1 and Wave 2...

Thanks to CIDRAP's Dr. Nicholas Kelley for asking the question of whether I'd looked at the epidemiology of the H7N9-related deaths between Waves 1 and 2.

So that led to the charts below.

Click on image to enlarge.
Only laboratory confirmed cases and the fatal cases with enough data to identify them are shown.
Wave 1 was defined as from weeks beginning 18-Feb-2013 to 20-May-2013.
Wave 2 as from Week beginning 7-Oct-2013, until today.
Top row: total cases; surviving and fatal.
Bottom row: fatal cases. Approximately 17 are missing sufficient data to identify.

If we look at numbers, because eyeballing these charts can be misleading we see some differences, although not huge.

The average age (in years) is divided as below:

• Wave 1
• All cases: 56.9
• Fatal cases: 64.5
• Wave 2
• All cases: 52.8
• Fatal cases: 63.0

The proportion of Males (%) is divided thus:

• Wave 1
• All cases: 72.0
• Fatal cases: 75.0
• Wave 2
• All cases: 66.3
• Fatal cases: 82.1

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H7N9 snapdate: age and sex pyramid for 227 laboratory confirmed cases

Click on image to enlarge.

Disease due to H7N9 infection is still most severe among males, as it was from very early on in the outbreak in 2013. 

Males comprise 68% of all cases.

The median age is 58-years and the median 54-years.

Click on image to enlarge.

If we follow some age bands with time we can see that since the last update 5-Feb, the 50-69-year age band has settled in as the most frequent source of H7N9 cases in China and a spike in younger cases occurs in the last week of Jan and 1st week of Feb.

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H7N9 snapdate: 316/317 cases by sex and week of onset/date reported

Click on image to enlarge.The dates along the bottom (x-axis) are the first Monday
of the week begging with that date. Week 1 is that in which
the first human case showed signs of disease.

A quick look shows that the proportion of recent female avian influenza A(H7N9) virus human cases is consistently sitting at or above 30%.

The overall proportion of females that have been H7N9 positive to date is 33% (316/317 cases with data). 

But over the most recent weeks, cases have often been a little more female than the 51-week average...

• Week 44: 50%
• Week 45: 50%
• Week 46: 31%
• Week 47: 33%
• Week 48: 45%
• Week 49: 35%
• Week 50: 30%
• Week 51: 39%

These weekly data are based on the week of disease onset (if known) or date reported (if disease onset unknown). Only time will tell whether the proportion of females drops back down again, or continues at higher levels than we saw in 2013. Such is the nature of an average number.

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H7N9 infection of women is not on the rise....

Click on image to enlarge.

A bit over a week ago I posted a chart showing that the proportion of females with avian influenza A(H7N9) virus may be rising.

We've had a lot of cases since then so is that trend still holding? 

[By the way, you are forgiven for  thinking this is the "H7N9 Down Under" blog!]

The new chart shows that the proportion of females has dropped back to something looking a little more like it did in 2013. The earlier data seems to have been a blip after all. 

With the addition of new cases to the dataset and with the shifting and re-sorting of cases into this or that week as onset data firm (WHO have recently been doing a fantastic job filling in the data gaps from Chinese reports), we can see that the proportion of females has been 40% or (often much) less each week for 10 of the past 14 (71.4%) weeks.  

In summary...

• The current proportion of female confirmed H7N9 cases overall is 29.5% (219/220 cases with data) 
• In 2013, females comprised 29.7% of cases
• In 2014 females comprise 29.5%. No difference to speak of.

So males dominate among the mostly severe human cases of H7N9 infection; business as usual for H7N9. 

Also, sustained person-to-person transmission (infected person passing to another  person, (1st round; = sporadic transmission) who passes it to another person (2nd round) and so on...is not happening.

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Middle East respiratory syndrome coronavirus (MERS-CoV) by sex...

Click on image to enlarge

I haven't updated my MERS-database since before Xmas. 

Wow.

It's painful to look at. 

Not because of a swag of new cases, I mean its tough to actually look at what's happening because the data, even with WHO expanding their coverage to include a more fixed set of information (the inclusion of animal contact is particularly welcome), is just so patchy. 

Some cases have sex but no date of onset of illness, some the other way around, hardly any have the date of lab confirmation or hospitalization and often it's near impossible to determine in which region the case was initially acquired. 

There is also still a question mark over the Tunisian cases and whether they originated in Tunisia or elsewhere I believe. The Spanish cases remain as probables (@WHO noted that they could not be confirmed via Twitter), so they are not on my list.

Nonetheless, I'll update my other charts as best I can. Keep an eye on the little bits of text in each graphic, they define the data gaps...164 of 177 possible total cases for example. In this instance, we are missing the sex of 13 MERS-CoV cases and I can only find identifying details for 73 of 75 deaths but 2 of those have no sex data either. You get the picture.

What is clear? Males (50% of those with data are >55-years of age) still dominate in the total cases and in those who have died of MERS-CoV infection (49% of male deaths are >55-years of age). That death is possibly due to exacerbation of an underlying disease or co-morbidity since they feature prominently in the MERS-CoV hospital-based population.

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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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H7N9 age with time: is a younger adult demographic emerging this time around?

This is a big graphic - sorry for that - but I thought it best to show the distribution of age bands (this is updated from the paper I co-authored recently with Joseph Dudley) alongside the shifting age in total numbers and proportion of cases each week. The data are all publicly sourced and verified against the WHO and scientific literature whenever possible and of course, against FluTrackers excellent case list.

1 case is lacking age data.

The chart below (click on it to enlarge and see much more clearly) then some comments underneath. Keep the previous sex/week chart in mind (it's trend has not changed much with the latest cases; these charts also result from a question from CIDRAP's Lisa Schnirring last Saturday) when looking at this. Is any effect seen below due to the increased female representation?

Click on image to enlarge.
It's probably more technically correct to use a line graph for (c) 
since a linked line implies that we know what happens in between 
each data point, but bars just don't show up clearly enough.

1. The median age of all H7N9 cases (surviving and fatal) is currently at 59-years; the mode is at 54-years.
2. The median age since Week 33 (see earlier post for why this number) is 54-years whereas from Week #1 to Week #32 it was 60-years. Is this a significant lowering of the median age in wave 2 or just because we're coming into Marc-April, where things may even out?
3. 74% of all cases are aged 40-years or older (M:F 1:2.36); 48% are 60-years of older (M:F 1:2.23); 6% are 20-years or younger (M:F 9:1)
4. The age band graph (a) looks very similar to that which we published in late 2013 using 136 avian influenza A(H7N9) virus cases (not at 175 cases)
5. The total numbers in graph (b) show that patients 20-years of age or younger have not yet shown up among the new wave of H7N9 cases, and if we look at the proportion of each age band each week (c), we can see that a younger than 60-year old demographic is predominating from December, as it did back in March and April 2013.

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H7N9 by sex and week...are female cases on the rise?

I tip the hat I'm not currently wearing to CIDRAP's excellent staff writer, Lisa Schnirring for the idea that led to this chart. 

Click on image to enlarge.

I've plotted 163 of the 164 lab-confirmed H7N9 cases (includes surviving and fatal cases) by the sex of the H7N9-positive person and the week in which they acquired their illness (if date of onset was noted), or else the date the case was reported to the world. 

The chart above shows that overall, male cases dominate the H7N9 landscape each week (69.5% of all cases are male)....except that among the new appearances of H7N9 in China, there seems to be a greater number of weeks in which females are equally represented among the cases. While the case numbers are low this still begs the question, as does the cause of the apparent start of the H7N9 season, what is driving these patterns?

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MERS-CoV cases by sex.

MERS-CoV cases by sex.

Larger versions and more detail can be found on the MERS-CoV page.

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Returning to the issue of H7N9 and its skewed presentations in the sexes.

I wrote about this on the 22.04.13 but forgot to mention that there are no accompanying descriptions of the societal roles of males and females in these areas, or in general. 

The skewing may reflect a bias towards the males simply because they could be more involved in activities that increase their risk of exposure to the influenza A(H7N9) virus host or its environmental source.

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H7N9 and the tendency for males to predominate in case and fatality numbers.

The H7N9 graphs highlight that cases and deaths are occurring in males more than females. We often see more males than females in hospital presentations for acute respiratory illnesses. Why this is so is not known for certain.

Published research from Prof John Upham in Queensland, Australia shows a difference in the immune response to rhinovirus, the virus responsible for triggering most asthma attacks, between males and females in that females stronger response cleans up the virus, probably related to sex hormones. 

This was supported by research from Dr Scotland in London, United Kingdom who found that female mice had more white blood cells and that these were more effective and less over-reactive than male cells in responding to invaders. 

Perhaps this can be extended to influenzavirus infections also.

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