Brazil's microcephaly and CNS disturbance (M&CD) monitoring: Report No. 22, 2016-Week No. 15...

These graphs are made using data obtained from Week 15's Brazil Ministry of Health microcephaly and foetal and infant microcephaly and central nervous system (CNS) disturbance (M&CD) report [1] and media report.[2]

The total number of suspected M&CD cases increased by 135 to 7,160 this week but those under investigation dropped by 95 to 3,741 this week - the fourth consecutive drop.

The chart above reports the number of newly suspected M&CD diagnoses in Brazil up to 16-April-2016. The cumulative curve (yellow dots; left hand axis) is steady and growing but not exponentially. This was a higher week (orange bars; right-hand axis) than last week but is among the smaller growth weeks.

In the graph above, we can see another big week (+175; blue bars; right hand axis) for suspected M&CD diagnoses that have been discarded upon closer investigation.The rate of these resolved diagnoses (line with blue dots, left-hand axis) continues to outpace the rate of confirmed microcephaly diagnoses (red dots, left-hand axis). The cumulative number of M&CD diagnoses does continue its climb this week (+55) despite two decreasing weekly totals (red bars; right-hand axis).

The number of these M&CD diagnoses to be confirmed with a Zika virus infection also continues its very slow climb (green dots; left-hand axis) also but has only risen by 3 new detections (green bars; right-hand axis) in this weeks report. That's the smallest rise since Week No.6. This maybe related to when testing is occurring. If it is too late after infection, then it will be negative. Although its not clear what samples are being tested nor whether form mum or baby.

References...

1. http://portalsaude.saude.gov.br/images/pdf/2016/abril/20/COES-Microcefalias---Informe-Epidemiol--gico-22--SE-15-2016--18abril2016--19h10.pdf
2. http://portalsaude.saude.gov.br/index.php/cidadao/principal/agencia-saude/23326-microcefalia-1-168-casos-foram-confirmados-em-todo-o-pais

Communicating science and medical research...

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Zika virus: ask questions....

The World Health Organization WHO) finally opened up the AskZika hashtag a week ago. Sadly, it has not been staffed to the extent that #AskEbola was, so little interaction is happening at this stage. 

Nevertheless, here are the first questions I asked...

Hi @WHO
Is 80% "asymptomatic #Zika" based on Yap island household study or something more recent?
How robust is the figure? #AskZika

— Ian M Mackay, PhD (@MackayIM) April 15, 2016

Hi @WHO,
s there *any* evidence for/against mild or subclinical #Zika cases having any viraemia? #AskZika

— Ian M Mackay, PhD (@MackayIM) April 15, 2016

Is there any correlation between *symptomatic* #Zika virus disease and pre-existing #Dengue virus antibodies? #AskZika

— Ian M Mackay, PhD (@MackayIM) April 14, 2016

Are there current investigations into animal reservoirs for #ZikaVirus in the Americas?#AskZika#Zika

— Ian M Mackay, PhD (@MackayIM) April 13, 2016

Are there yet any confirmations of which mosquito species (single and plural) carry #ZikaVirus in the Americas? #AskZika#Zika

— Ian M Mackay, PhD (@MackayIM) April 13, 2016

.@MackayIM because people get infected early in life and are then immune?

— Ian Goodfellow (@igoodfel) April 13, 2016

Thanks to Ian for reminding me of this likely reason to address the last question - I had a caffeine-free moment when asking this one! 

Because Zika virus has been ticking along for over 60 years - that we know of - in African countries - the population of affected areas will already have some degree of immunity by due to constant exposures, which the current thinking says are unnoticed 80% of the time. My Yap island question above highlights my doubt about that figure though. 

But Ian's response made me think - do we know that an asymptomatic or mild Zika virus infection of a women produces enough immunity, and/or immunity of the right kind, to ensure that if she becomes infected by Zika virus a second time and she is pregnant, she could not deliver a child with central nervous system disease? We don't. Presumably, even with a population that has "seen" more Zika virus circulating, there would still be cases of adult women being infected for the first time and, if Zika virus is the cause, microcephaly resulting. Perhaps this has simply been lost in the background health issues though. Or perhaps something special, different or more complex is happening in Brazil that goes beyond Zika virus infection+pregnant woman=rare microcephaly case.

Congenital Zika syndrome is not reliably distinguished from other infective, toxic, or genetic causes of congenital anomalies, although others say the anomalies attributed to Zika virus infection outside the central nervous system are distinctive. This disagreement alone highlights how many questions this outbreak has raised and how few answers we've received. 

Do you have questions about all this? Pose them to the #AskZika channel. Maybe we'll get some answers soon. We may at least get the scientific consensus of some answers, if that is satisfying enough for you.

Colombia timing update...

Colombia actually removed a Zika virus positive mother from the number of microcephaly cases this past reporting week. 

Two cases still remain and there have now passed 186 days (6mths 3days) since Colombia reported it's first local Zika cases (16OCT2016).

Remembering that Brazil first reported positive (but unconfirmed) laboratory tests for Zika virus disease on 29APR2015 and started reporting foetal anomalies on the rise (n=141), in the form of microcephaly, 30OCT2015 (184 days, or 6 months later)

Mosquito repellents and personal protection...

Want to tell someone what to use to avoid mosquito bites, repel mozzies and treat bites? Refer them to this little gem from Dr Cameron Webb (@Mozziebites on Twitter).

You can see it on the website here and download the PDF here.

References...

1. https://cameronwebb.wordpress.com/mosquito-repellent-guidelines/
2. http://medent.usyd.edu.au/RepellentGuidelines.pdf

Colombia Zika virus report, Week No. 14...

The latest epidemiological report, which includes data on Zika virus disease (ZVD; 03APR2016-09APR2016), has been produced by the Colombian National Institute for Health team.[1]

Graph No.1. The cumulative curve of confirmed ZVD cases
(green circles, left-hand axis) and the change in confirmed ZVD case
numbers when compared to the preceding week's total
(green bars, right-hand axis). Data from [1].
Click on graph to enlarge.

Graph No. 1 shows a smaller week than last week, with the addition of 231 new laboratory confirmed Zika virus (ZIKV) detections. 

Graph No.2. The cumulative curve of suspected ZVD cases 

(pink circles, left-hand axis) and the change in suspected ZVD case 

numbers when compared to the preceding week's total 

(red bars, right-hand axis). Data from [1]. 

Click on graph to enlarge.

Graph No. 2 has been made to show the change in suspected cases. Most of these are not laboratory confirmed, but (I'm presuming here) include those that were from Graph No. 1.

Graph No.3. The cumulative curve of confirmed ZIKV infections 

(lilac circles, left-hand axis) and the change in confirmed ZIKV infection 

numbers when compared to the preceding week's total 

(purple bars, right-hand axis). Now added the reported umber of microcephaly cases confirmed as ZIKV infected (yellow bars, right-hand axis). Data from [1]. 

Click on graph to enlarge.

Graph No. 3 shows that to Week No. 14, 10,674 suspected and 1,706 confirmed ZIKV infections have been identified in pregnant women. As of this report, 2 (decreased by 1 from last week) live births have been diagnosed with with microcephaly and were reported as being ZIKV positive; 15 (down from 30) other microcephaly diagnoses are under investigation.[1,2]


References...

1. http://www.ins.gov.co/boletin-epidemiologico/Boletn%20Epidemiolgico/2016%20Boletin%20epidemiologico%20semana%2014.pdf
2. https://www.minsalud.gov.co/Paginas/Colombia-confirmo-dos-primeros-casos-de-microcefalia-asociados-a-zika.aspx

Brazil's microcephaly and CNS disturbance (M&CD) monitoring: Report No. 21, 2016-Week No. 14...

These graphs are made using data obtained from Week 14's Brazil Ministry of Health microcephaly and foetal and infant central nervous system (CNS) changes report, which you can also find here.

The chart above reports another quiet week in terms of the number of newly suspected microcephaly cases in Brazil up to 09-April-2016. The cumulative curve of suspected diagnoses of microcephaly and CNS disturbance (M&CD) continues to flatten, showing that slowing, but in different visual way.

In the graph above, we can see another big week (blue bars; right hand axis) for suspected M&CD diagnoses that have been discarded upon closer investigation. 

The rate of these (line with blue dots, left-hand axis) has been outpacing the rate of confirmed microcephaly diagnoses (red dots, left-hand axis) lately, perhaps suggesting that the whole process is flowing a little better? But the cumulative number of confirmed M&CD diagnoses (red dots) does keep climbing each week-let's be clear on that point.

The number of these M&CD diagnoses to be confirmed with a Zika virus infection continues its slow climb also. Allowing for an absence of sampling earlier on, I presume this curve is now not keeping pace with current microcephaly confirmations because there are also other causes of microcephaly in the region? Or testing is not occurring on all samples. Or something else.

The Table above is excerpted from the Pan American Health Organization (PAHO) and World Health Organization (WHO) epidemiological update to 14-Apr-2016.[2] 

It lists the number of confirmed microcephaly diagnoses occurring in relation to Zika virus infected women. But place the Brazil figure in the context of there being 189 laboratory confirmed diagnoses - and place that in the context of...many things that remain very unclear beyond vague statements of poor capacity, the ongoing faith in clinical syndromic diagnostic wonderfulness and the overwhelming impact of scientific consensus on all aspects of this event.

References...

1. http://portalsaude.saude.gov.br/images/pdf/2016/abril/12/COES-Microcefalias---Informe-Epidemiol--gico-21--SE-14-2016--12abril2016--11h24.pdf
2. http://www.paho.org/hq/index.php?option=com_content&view=article&id=11599&Itemid=41691&lang=en

A line is about to be crossed...

Colombia has already reported over 30 cases of congenital foetal anomalies in 2016. This is not outside the "normal range" for such disease - at the moment.[4]

From [4].

However, there are over 1,500 hundred laboratory confirmed Zika virus infected pregnant women in Colombia -  over 10,200 if you don't worry about laboratory confirmation.

Why am I telling you this?

Because a line in time is about to be crossed.

Brazil first reported reported positive (but unconfirmed) laboratory tests for Zika virus disease on 29th April 2015. Brazil then started to report a rise in foetal anomalies (an initial 141), in the form of microcephaly on 30th October 2015. This was 184 days - or about 6 months later.[1]

Zika virus was first confirmed in Colombia on 16th October 2015. Today, 12th of April 2016, is 179 days, or about 6 months later.[1] Colombia is currently carrying the next biggest load of Zika virus disease cases, after Brazil.[6]

It would be incredibly dense of me to suggest that at exactly 184 days a whole lot of babies with microcephaly and a host of brain injuries will suddenly be born. However, we are about to cross a significant line after which we may see a steady and continuous increase in birth defects, well above the expected averages, accruing in Colombia. This is no proof, but will greatly add weight to the case for Zika virus infection causing such anomalies if it happens. 

Growing Zika virus case number trends in dark blue
From PAHO-WHO [5]

It would also be stupid of me to suggest that the rate or the total numbers of diagnoses will be directly comparable to those in Brazil. Because we have very little testing data to use to compare between Colombia (lots) and Brazil (hardly any as can be seen by lack of Brazil graphics in recent PAHO-WHO report[5]), we don't really know how well Zika spread has been captured. Is Zika virus focal, widespread, ongoing (see map for Colombia above that suggest it is), decreasing, what was it when the first laboratory confirmation occurred, what is like now...? 

We also don't know how closely the first reported detections of Zika virus correlates with the first actual cases of infection in the two countries nor who fast new cases spread.

Then, there's that hint that perhaps there is as much as a 2 month delay in reporting Zika virus positives in Colombia; factor that into the timeline above.[3]

But from here on in, watch Colombia closely.

References...

1. http://who.int/bulletin/online_first/16-171082/en/
2. http://who.int/…/zika-vir…/zika-historical-distribution.pdf
3. http://virologydownunder.blogspot.com.au/2016/04/colombiano-recent-confirmed-zika-virus.html
4. http://virologydownunder.blogspot.com.au/2016/04/colombia-zika-virus-report-week-no-13.html
5. http://www.paho.org/hq/index.php?option=com_content&view=article&id=11599&Itemid=41691&lang=en
6. http://www.nature.com/news/first-zika-linked-birth-defects-detected-in-colombia-1.19502

Zika virus: the scientific consensus of opinion...

And this right here,  is why we can't have nice (..data-based discussions about associating...) things kids...

This is great. Rémi Charrel on 200 most recent #zika papers. Opinion/review : empiric data = 4:1
#ECCMID2016 pic.twitter.com/ZSjekCyGje

— David Fisman (@DavidFisman) April 11, 2016

Tweeted from a talk presented at 2016's European Congress of Clinical Microbiology and Infectious Diseases (ECCMID).
So that "scientific consensus" on Zika virus causing microcephaly appears like it's a consensus of...opinion at the moment.  

Thankfully, there are some good papers amongst that basic research. Some.

Colombia...no recent confirmed Zika virus positives or reporting lag or...?

UPDATE #1: 24APR2016

Okay. Let me rephrase an issue I had from one of my posts yesterday-the one looking over the Colombian data. The relevant text was...

"I'm still not clear how the tally of confirmed cases is rising, but not showing up on the Colombian NIH graph (the red bars; the grey ones are clinical suspected cases). 

I've excised and posted the Colombian NIH graph to the left. 458 cases this week should show up clearly using that axis - it was the second biggest tally, just below Week No. 8 (also missing?) and 1.6X bigger than Week No. 4 which has been plotted and shows up clearly. I'm just assuming that the graph person has forgotten but would love to know if there is something else going on."

Below I've excised the relevant graphs from the most recent epidemiology report (Week No. 13 [2]) and also the one that first plotted confirmed alongside suspected Zika virus (ZIKV) cases (Week No. 11 [1]).

You can in fact see that the red bars have grown over the 3 week period - but that none of the 700 confirmed cases reported over that time have visibly made it into a bar after Week No. 5. So my question is whether that means:

1. no newly confirmed ZIKV cases have been detected/become ill during the past 8 epidemiology weeks (keeping in mind that Week No. 13's report only reports data to 02APR2016)
2. there is an 8-week lag in getting lab data into these reports?
3. Someone forgot to update the graphs
4. Colombia is no longer testing for ZIKV

 ..or perhaps something else altogether?

Week No. 11.
Data from [1]

Week No. 13.
Data from [2]

The lag seems to be the leading theory so far (see Tweet below)...but that's quite a lag. 

@MackayIM @INSColombia graph reflects adjusted reported cases per wk. not #s on table. "New" confirmed may be old. Wk12 only 1,100 on graph

— Gabby Molinolo (@gabby_molinolo) April 10, 2016

I find it strange that no-one seems to be critical of the testing lag here and yet it was the topic du jour for MERS in the Kingdom of Saudi Arabia. 

Is it simply about the perception of resources - the Americas are perceived as resource-poor and the Saudis as resource abundant? 

In the area of lab testing, I'm not at all convinced that the Saudis were at all resource rich though. I don't think they were in any better position at the start of their outbreaks. Especially if the resource we measure is understanding about testing to understand the aetiology of an emerging infectious disease.

References...

1. http://www.ins.gov.co/boletin-epidemiologico/Boletn%20Epidemiolgico/2016%20Bolet%C3%ADn%20epidemiol%C3%B3gico%20semana%2011.pdf
2. http://www.ins.gov.co/boletin-epidemiologico/Boletn%20Epidemiolgico/2016%20Bolet%C3%ADn%20epidemiol%C3%B3gico%20semana%2013.pdf

Updates...

1. Added a new 3rd option which was not carried over from the orginal post 10APR2016  - and pushed the previous 34rd to 4th