Wednesday, 25 May 2016

How are scientists responding to the threat of mosquito-borne viruses?

Photo courtesy of Dr. Sonja Hall-Mendelin, Forensic
and Scientific Services, Department of
Health, Queensland.
We tried something different this week. 

Dr. @kat_arden, Dr Sonja Hall-Mendelin and myself wrote a story trying to give you a taste of what goes on, kinda behind the scenes, in Queensland, the only State in Australia that has the two tiny bads - Aedes aegypti and Aedes albopictus. Also the State with the greatest number of detected human Zika virus infections in travellers.

So, thanks to the foresight of the crew at Croakey, we have been able to briefly touch on the hard work done by Queensland's many innovative and agile scientists, medical doctors, entomologists, council workers, response teams and other collaborators whom I've undoubted and very unintentionally failed to list.

If you like the story - see the link below - please tweet it, facebook it and send it to your family and friends. This may lead to more of these kinds of pieces in the future - but only if you like them.

This was written for the community.

Brazil's microcephaly and CNS disorder (M&CD) monitoring: Report No. 27, 2016-Week No. 20...

These graphs are made by me using data obtained from epidemiological week (EW) number 20's Brazil Ministry of Health microcephaly and foetal and infant microcephaly and central nervous system (CNS) disorders (M&CD) report.[1]

Brazil last reported a total of 120,161 suspected Zika virus detections some weeks back. Around one thousand of these have been portability confirmed.[2]


Suspected M&CD cases...

The total number of suspected M&CD cases increased by 89 to 7,623 this EW (compared to last).

The graph above shows the number of suspected M&CD diagnoses in Brazil up to 21-May-2016. The cumulative curve (yellow dots; left hand axis) is growing, but slowly.

This was another slower weekly rise (orange bars; right-hand axis). These bars are based on the difference in total suspected cases reported this EW compared to that reported in the last EW. This method may not reflect the diagnoses that occurred during the past EW (some may have come from days or weeks earlier), but that level of detail is not available in the MOH report.


Confirmed and discarded M&CD diagnoses...


M&CD cases under investigation decreased by 75 to 3,257 this week - the ninth consecutive decrease.


In the graph above, we can see that 114 (blue bars; right hand axis) suspected M&CD diagnoses were discarded upon closer investigation with a current total of 2,932 removed.

The rate of these resolved diagnoses (line with blue dots, left-hand axis) continues to outpace the rate of the smaller overall number of confirmed M&CD diagnoses (red dots, left-hand axis).

As of this EW, 19% of suspected M&CD diagnoses have been confirmed while 38% of suspected diagnoses have been discarded-a percentage that has increased for 16 weeks.

The cumulative number of confirmed M&CD diagnoses does continue its climb this EW, growing by 50 new diagnoses (red bars; right-hand axis) to total 1,434.




The number of these M&CD diagnoses to be confirmed with a Zika virus infection also grows (green dots; left-hand axis) by 1 new detection (green bars; right-hand axis) to 208 this EW.

Those confirmed Zika virus infections represent 15% of all confirmed M&CD diagnoses and 3% of all suspect diagnoses.

Monday, 23 May 2016

Brazil's microcephaly and CNS disorder (M&CD) monitoring: Report No. 26, 2016-Week No. 19...

These graphs are made by me using data obtained from epidemiological week (EW) number 19's Brazil Ministry of Health microcephaly and foetal and infant microcephaly and central nervous system (CNS) disorders (M&CD) report.[1]

Brazil last reported a total of 120,161 suspected Zika virus detections some weeks back. Around one thousand of these have been portability confirmed.[2]

Suspected M&CD cases...

The total number of suspected M&CD cases increased by 96 to 7,534 this EW compared to last.

The graph above shows the number of suspected M&CD diagnoses in Brazil up to 14-May-2016. The cumulative curve (yellow dots; left hand axis) is growing, but slowly.

This was another slower weekly rise (orange bars; right-hand axis). These bars are based on the difference in total suspected cases reported this EW compared to that reported in the last EW. This method may not reflect the diagnoses that occurred during the past EW (some may have come from days or weeks earlier), but that level of detail is not available in the MOH report.

Confirmed and discarded M&CD diagnoses...

M&CD cases under investigation decreased by 101 to 3,332 this week - the eighth consecutive decrease. This may be occurring for a range of (guessed) reasons including:
  • improved capacity to address a large volume of request for clinical classification of suspect diagnoses.
  • streamlining the confirmation processes
  • retrospective application of changed head circumference definitions resulting in reductions to the number of the microcephaly diagnoses.
    This aspect will not reduce the number of cases with structural brain changes that occur in the absence of a decreased head size - which are reportedly also related to Zika virus and/or other causal influences.
    There is time involved in making these diagnoses because of the need for detailed ultrasound and other diagnostic investigations to identify congenital infection outcomes including intracranial calcifications, dilation of cerebral ventricles or posterior fossa changes and other issues.
In the graph above, we can see that 139 (blue bars; right hand axis) suspected M&CD diagnoses were discarded upon closer investigation with a current total of 2,818 removed.

The rate of these resolved diagnoses (line with blue dots, left-hand axis) continues to outpace the rate of the smaller overall number of confirmed M&CD diagnoses (red dots, left-hand axis). 

As of this EW, 18% of suspected M&CD diagnoses have been confirmed while 37% of suspected diagnoses have been discarded-a percentage that has increased for 15 weeks

The cumulative number of confirmed M&CD diagnoses does continue its climb this EW, growing by 58 new diagnoses (red bars; right-hand axis) to total 1,384

The number of these M&CD diagnoses to be confirmed with a Zika virus infection also grows (green dots; left-hand axis) by 2 new detections (green bars; right-hand axis) to 207 this EW

Those confirmed Zika virus infections represent 15% of all confirmed M&CD diagnoses and 3% of all suspect diagnoses - but these are not fair comparisons for a range of reasons I won't go on about here.

References...

  1. http://portalsaude.saude.gov.br/images/pdf/2016/maio/18/Informe-Epidemiol--gico-n---26--SE-19-2016--16mai2016-19h00.pdf
  2. http://combateaedes.saude.gov.br/images/sala-de-situacao/informe_microcefalia_epidemiologico26.pdf

Sunday, 22 May 2016

Zika in the mouse...

Just over a week ago there were a few published Zika virus (ZIKV) studies in mice and brain balls (neurospheres and organoids). These were big deals. One was a letter to Nature by Cugola and colleagues, describing defects in the brains of mouse pups after their mothers were infected with virus.[1] This was one big letter and well outside my expertise to review in any sort of depth. But it raised a few questions for me.

Briefly, there were two parts to the letter - in part 1, two lines of pregnant mice (SJL and C58BL/6) were injected with virus and the pups evaluated immediately after birth. In Part 2, cell culture created human progenitor stem cells (hPSCs) and brain balls (neurospheres and cerebral organoids) were incubated with ZIKV.

This study included a ZIKV variant currently circulating in Brazil (ZIKVBR) rather than using the virus from six decades ago, but disappointingly, it did not include dengue virus or Chikungunya virus as control viruses against which to compare the activities described for ZIKV. There was some use of a slow-growing, attenuated (low risk of nerve pathology) vaccine strain of yellow fever virus as control virus - but exactly how wasn't clear to me. There was no virus control in the mouse work though - just the organoid experiments - as far as I can tell.
  1. One big takeaway message was that the C56BL/6 pups did not have any notable differences compared to healthy pups. Virus did not seem to cross the placenta. All the problems found were in the other line of mice - the immunologically defective SJL.[8,9]
    The authors note the C56BL/6 line had a robust antiviral immune response.
    If ZIKV is indeed the cause of congenital disease in humans, there is something to that result that should be of much interest. Whether that is at the level of a genetic immune deficiency, a microbiome-level issue or the occurence/history, absence or order of past infections, among other things, is unclear
  2. The SJL pups were smaller, had lots more ZIKV RNA in the brain than in kidney, liver or spleen, tissues, had eye abnormalities and had elevated markers suggesting that brain cell death was linked to apoptosis and autophagy. The authors remarked how these shared similarities with foetal human disease
  3. I have my usual question about how relevant to a human is a model that directly introduces a dumpload of virus into the blood (40,000,000,000 plaque forming units) by injection when the natural route of infection of a human is considered to be mostly due to a (presumably) much lower load from mosquito bite. Adding the same dose of inactivated ZIKV would have been very interesting to test for non-viral effects from the inoculum (h/t KatA)
  4. Human pluripotent stem cell (hPSC)-derived neural progenitor cells (NPCs) were also exposed to virus and found to die via apoptosis. But where did these cells originate? I can't tell from the methods and references cited. Was it from human skin cells as other experiments have used? Skin cells are known to host ZIKV [3] Could this be a confounding factor? 
  5. Mock infected NPCs - "pretend" infection in the absence of any actual virus to check whether the method or material carrying the virus caused the observed damage - actually upregulated expression of the likely receptor for ZIKV, AXL, but ZIKV infection didn't.  Does that mean ZIKV down-regulated expression caused by something in the mock inoculum?
  6. High doses (10 MOI) of ZIKV killed NPCs, but a lower dose (1 MOI) did not - what does that mean for the heavily dosed mouse model; and for a human bitten by a mosquito? ZIKVBR and an African lineage ZIKV (ZIKVAF) acted similarly. 
  7. In three dimensional cultures, neurospheres growing in the presence of 10 MOI of ZIKVBR were smaller and cell death was apparent - the effect was not as strong with ZIKVAF suggesting lineage differences. Effects were dose dependent - stronger with higher doses (10 MOI) than lower (1 MOI). Differences between ZIKV lineages is something yet to be fully explored by virology-for some inexplicable reason(s).
You'll possibly have noticed two units used by the authors - plaque forming units and MOI (multiplicity of infection). These are different because of different methods used to determine the endpoints. Briefly (but still technically):

From Sloutskin et al.[6]
  • For plaque-forming units (PFU) - we titrate infectious virus that can damage cells (make plaques) and look at where the effect finishes. By titrate I mean serially dilute and then add each diluted solution to a separate well of the same cells, usually grown in a multiwell plate. The effect is the formation of plaques - areas of clearing due to virus-induced death of cells that had first been grown into a single layer in each plate well before being infected by a virus preparation. The dilution before the effect finishes is the PFU.
    There are also issues around how well PFU value determined using one cell culture model holds up when infecting a cell/tissue/organ/animal that is different from the one you determined your PFU on - you may get different results.
    For example you may find your virus preparation contains 10,000 PFU on the original cells, but if you did that same titration with the same preparation but using a different cell type, it may contain 100,000 PFU or 1,000 PFU.
    In the study above, ZIKV was grown up using a C6/36 mosquito cell line, then titrated using porcine kidney epithelial cells to determine the PFU then that C6/36 preparation was used for the mouse, NPC, neurosphere and organoid incubations. This is normal approach but can raise questions.
  • For multiplicity of infection (MOI) we are talking about the average number of virus particles in a preparation that infect a target cell. 1 MOI means 1 virus particle per cell. An MOI of 10 means 10 virus particles per cell.[4] This works well in cell culture where we often use a single cell type grown in a single layer - conditions, viral density and culture volumes are optimized and we use the same cells as for the PFU.[5] When you take that MOI of 1, calculated on your cell line, and add it to a different and complex tissue, or animal, with lots of different cell types, perhaps spread over a larger or smaller surface, in the presence or absence of an antiviral response, with more or fewer receptors etc...the ratio of 1 virus : 1 cell will probably not hold up. So using a higher MOI makes it more likley that each cell in a different tissue/organ/animal will get infected. Thus an MOI of 1 and 1 PFU are not always the same thing. A virus preparation determined to have an MOI of 1 using one system might require 0.1 or 273.64 PFU of that preparation in another cell/tissue/organ/animal system, because it takes that amount to finally show the desired effect (cell death, PCR positivity, virus protein detection etc) in that target cell/tissue/organ/animal.

    We should also think about how relevant an MOI of 10 is to the thing we originally sought to study. In this case it is the early brain structure of a foetus whose mother was infected from a mosquito bite.
    The bite itself would not have delivered anything like an MOI of 1 to any tissue in that mother's body.
    But how much ZIKV crosses the human placenta in the rare cases that it does at all? Well, we assume placental crossing is a rare event for ZIKV.
    I'd presume it's also not an MOI of 1 for any tissue in the foetus - unless the placenta is where the virus is being amplified. But it does seem like there is a lot of ZIKV in the brain of studied infected foetuses.  So this mouse model might reflect what happens in a forming human brain that amplifies virus it acquired after placental crossing, or that was present from conception (here for more on that theory[7]).  

One of my biggest questions about this study is - so what? 

This is an incredibly dense and impressive piece of work - don't get me wrong. It may well be the definitive result that so many have commented on it being. But I wonder if the same degree of very detailed investigation gone into the study of other mosquito-borne viruses in mouse brains? Have we sought out the congenital infection potential of other arboviruses in mouse pups and investigated arbovirus impact on neurospheres and organoids to this extent? Are these results unique to ZIKV or do the same or similar effects from other viruses, that - to our knowledge - are not considered threats for congenital disease in humans? We should probably establish that, by using more experimental controls, before we continue on our journey along this limb.

I have trouble saying that this experiment equals that disease as much as I am troubled by saying that the (possible) surge of microcephaly diagnoses in north east Brazil is caused by that particular parallel viral epidemic.

References...
  1. The Brazilian Zika virus strain causes birth defects in experimental models
    http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature18296.html
  2. http://jvi.asm.org/content/82/12/6024.full
  3. http://www.ncbi.nlm.nih.gov/pubmed/26085147
  4. https://en.wikipedia.org/wiki/Multiplicity_of_infection
  5. http://www.virology.ws/2014/05/06/virology-question-of-the-week-what-matters-more-multiplicity-of-infection-or-virus-concentration/
  6. http://www.bio-protocol.org/e1295
  7. http://virologydownunder.blogspot.com.au/2016/04/the-three-parent-hypothesis-mum-dad-and.html
  8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1453197/
  9. http://www.informatics.jax.org/external/festing/mouse/docs/SJL.shtml

Tuesday, 17 May 2016

27 countries have seen a MERS-CoV case with Bahrain's addition...

13 of those 27 have had local transmission.

The Bahrain-diagnosed infection was likley acquired from a camel in his dromedary camel farm in Saudi Arabia.

Click to enlarge.

Sunday, 15 May 2016

Colombia Zika virus report, Epidemiological Week No. 18...

The latest epidemiological report, which includes data on Zika virus disease (ZVD; 01MAY2016-07MAY2016), 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 that 1,116 more laboratory confirmed cases of ZVD were reported this week than last. That's the biggest weekly rise on record. The total now at 4,867 or 7% (reaching the highest proportion reported to date) of all the clinically suspected Zika virus (ZIKV) detections.
Graph No.2. The cumulative curve of suspectedZVD 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 shows the change in suspected cases. These are not laboratory confirmed. The suspected ZVD cases continue to rise in a linear fashion, adding 2,665 this week to total 71,299 suspected cases of ZVD. This is far from the biggest weekly rise suggesting the figure above may indicate more testing or improved laboratory capacity or reporting (clearing a backlog?).
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). To account for adjustments 
that take cases away when there is no weekly case growth, a negative 
value - the y-axes now allow for negative values. Data from [1]. 
Click on graph to enlarge.
Graph No. 3 shows that to Epidemiological Week No. 18, 11,417 suspected (-307 compared to last week) and 2,948 confirmed ZIKV infections (+941 - biggest rise to date) have been identified in pregnant women. 

As of this report, 5 (same as last week) live births have been diagnosed with microcephaly/central nervous system disorders and were reported as being ZIKV positive; 43 (up from 32 last week-fourth week to increase in total number) other microcephaly diagnoses are now under investigation.[1] That represents 0.17% of all confirmed ZIKV positive mothers (down from 0.25% last week).

It has now been 210 days, or about 7 months, since ZIKV was first confirmed in Colombia on 16th October 2015.[2] Colombia is currently carrying the next biggest load of Zika virus disease cases, after Brazil.[3] Keep in mind that when talking about microcephaly - we have to think back in time to what insult or infection might have occurred in the first or second trimester. The counts of virus occurring this week will have zero impact on what happened back then.

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.[4]

References...

  1. http://www.ins.gov.co/boletin-epidemiologico/Boletn%20Epidemiolgico/2016%20Boletin%20epidemiologico%20semana%2018.pdf

Thursday, 12 May 2016

Zika index: VDU's posts on Zika...

To make it a little easier for me to keep up and to look back at the crazy assumptions made during the 'fog of outbreak', I thought an index of some of my Zika virus (ZIKV)-related posts - would be useful.
  1. What does it mean when one twin gets a disease and the other doesn't? The media reposts on a new twin study in Brazil.
    Zika, twins and complexity...http://virologydownunder.blogspot.com.au/2016/05/zika-twins-and-complexity.html
    08MAY2016
  2. The first ZIKV-containing epidemiology report, not focussed on microcephaly, from Brazil. But little detail and more questions raised about clicnial diagnosis to described a poorly lab-supported epidemic.
    Zika virus (ZIKV) disease in Brazil (not just microcephaly) gets its own report...kindahttp://virologydownunder.blogspot.com.au/2016/04/zika-virus-zikv-detection-in-brazil-not.html
    29APR2016
  3. Review of the first report of vertically acquired foetal ZIKV with detection of viral RNA in amniotic fluid and some further questions.
    Zika virus in amniotic fluid...but is that enough?http://virologydownunder.blogspot.com.au/2016/01/zika-virus-in-amniotic-fluidbut-is-that.html
    09JAN2016

Wednesday, 11 May 2016

Colombia Zika virus report, Epidemiological Week No. 17...

The latest epidemiological report, which includes data on Zika virus disease (ZVD; 24APR2016-30APR2016), 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 that 1 fewer laboratory confirmed case of ZVD was reported this week than last. That's different. The total now at 3,751 or 5% of all the clinically suspected Zika virus (ZIKV) detections.

Graph No.2. The cumulative curve of suspectedZVD 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 shows the change in suspected cases. These are not laboratory confirmed. The suspected ZVD cases continue to rise in a linear fashion, adding 2,671 this week to total 68,634 suspected cases of ZVD.
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). To account for adjustments 
that take cases away when there is no weekly case growth, a negative 
value - the y-axes now allow for negative values. Data from [1]. 
Click on graph to enlarge.
Graph No. 3 shows that to Epidemiological Week No. 17, 11,724 suspected (+418) and 2,007 confirmed ZIKV infections (-1) have been identified in pregnant women. 

As of this report, 5 (an increase (+1) from last week) live births have been diagnosed with microcephaly/central nervous system disorders and were reported as being ZIKV positive; 32 (up from 26 last week) other microcephaly diagnoses are now under investigation.[1] That represents 0.25% of all confirmed ZIKV positive mothers.

It has now been 207 days, or about 7 months, since ZIKV was first confirmed in Colombia on 16th October 2015.[2] Colombia is currently carrying the next biggest load of Zika virus disease cases, after Brazil.[3]

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.[4]

References...

  1. http://www.ins.gov.co/boletin-epidemiologico/Boletn%20Epidemiolgico/2016%20Bolet%C3%ADn%20epidemiol%C3%B3gico%20semana%2017.pdf
  2. http://www.who.int/bulletin/online_first/16-171082/en/
  3. http://www.nature.com/news/first-zika-linked-birth-defects-detected-in-colombia-1.19502
  4. http://who.int/bulletin/online_first/16-171082/en/

Sunday, 8 May 2016

Zika, twins and complexity...

The media reported yesterday on a study underway in Sao Paolo, southern Brazil.[1] The study is looking at five pairs of twins so far - each pair includes one with a diagnosis of microcephaly, and one borne completely healthy. There is no detail on whether any less externally obvious Zika virus related central nervous system (CNS) disease has been sought so far.


From the Australian twin registry website.[8]
In the case discussed in the article, the mum of one such set of twins recalled symptoms of a Zika virus-like infection early in her pregnancy.[1] As you can see in the image to the right (and read at the linked website[8]), "twins" is a pretty broad description. It isn't hard to see how even one monozygotic twin (MZ twins develop from an egg fertilized by a single sperm) that one could become infected when another wasn't. This may be informative to the Three Parent Hypothesis.[9]

With around 3 million live births a year (roughly 8,500 live births average per day; 360 an hour [11]), there is likely to be a goodly number of twins when around 1.5% to 3.4% of live births result in twins of some type.[2,3]

I'm clearly no expert in the area of obstetrics, neonatology or congenital central nervous system disorders. But this finding, certainly not the first or only disease/healthy split between twins of this sort,[4,5,6,7] is fascinating.

To me, this finding highlights how rare the microcephaly and CNS disorder outcome seems to be after a suspected Zika virus infection of a mum at some point in her pregnancy. With so many births and just 1,300 M&CD diagnoses, its clearly nothing like as simplistic as "Zika virus infection while pregnant results in microcephaly".


A visualization some of the things that may have to occur for a maternal
Zika virus infection to result in an M&CD diagnosis.
This assumes that a mother's 
rash/fever/joint pain illness at some
time in her pregnancy prior to delivery, was due to Zika virus and
not one of the many other possible causes of such non-specific illness. 

The order of everything in  the grey box - which is not an exhaustive
list - is not intended to carry any meaning.
It is to indicate that there seem to be a large 
range of things
that must occur in a certain order, at a certain time, at a certain
strength or for a certain period of exposure, for the final outcome of
M&CD to occur in a newborn infant, or aborted foetus. 

It may be a different mix that results in different Zika virus-related
disorders - or even in M&CD in one infant compared to the next. 
What is for sure though, is that sometimes release of preliminary Zika virus disease study data without more detail and discussion, can give the appearance that things are more simple than they are.

The following tweets were a result of listening to Dr Celina Turchi Martelli, of the Brazilian Ministry of Health’s Fundação Oswaldo Cruz Foundation (FIOCRUZ)-Pernambuco, Brazil.[10] 

She gave a little insight into two case-control studies she is involved in, while speaking to the Cura Zika symposium hosted by The University of Pittsburgh.[10]


In response to those, Dr Andrew Lover crunched some numbers and highlighted that those data, when viewed in isolation, suggest that a Zika virus infection alone is almost guaranteed to result in microcephaly. 
But that is clearly not the case. Remember that total of 1,300 confirmed M&CD diagnoses amidst 8,500 live births a day? It was very probably not the intended meaning of Dr Martelli either. 

This all just exemplifies how confusing the Zika virus epidemic can be to the public, how complex finding a cause(s) to the M&CD surge will be and how much time may yet pass before we get anywhere near that goal. 

It's all a bit confusing for scientists too!

References...
  1. http://www.reuters.com/article/us-health-zika-twins-idUSKCN0XX1V2
  2. .https://www.twins.org.au/twins-and-twin-families/about-twins/facts-and-figures
  3. http://www.cdc.gov/nchs/fastats/multiple.htm
  4. http://learn.genetics.utah.edu/content/epigenetics/twins/
  5. http://www.ncbi.nlm.nih.gov/pubmed/7847025
  6. http://www.nature.com/pr/journal/v61/n5-2/full/pr2007129a.html
  7. https://www.technologyreview.com/s/406200/when-only-one-twin-gets-a-disease/
  8. https://www.twins.org.au/twins-and-twin-families/about-twins/facts-and-figures
  9. http://virologydownunder.blogspot.com.au/2016/04/the-three-parent-hypothesis-mum-dad-and.html
  10. https://pitt.hosted.panopto.com/Panopto/Pages/Viewer.aspx?id=a9abb64a-6f84-43d3-ac50-144b96fe67a4
  11. http://countrymeters.info/en/Brazil

Saturday, 7 May 2016

Brazil's microcephaly and CNS disorder (M&CD) monitoring: Report No. 24, 2016-Week No. 17...

These graphs are made by me using data obtained from epidemiological week (EW) number 17's Brazil Ministry of Health microcephaly and foetal and infant microcephaly and central nervous system (CNS) disorders (M&CD) report.[1]

Brazil reports a total of 120,161 suspected Zika virus detections this EW.[1] Around one thousand of these have been laboratory confirmed.

Suspected M&CD cases...

The total number of suspected M&CD cases increased by 115 to 7,343 this EW.


The graph above shows the number of suspected M&CD diagnoses in Brazil up to 30-April-2016. The cumulative curve (yellow dots; left hand axis) is growing, but slowly. 

This was another slower weekly rise (orange bars; right-hand axis). These bars are based on the difference in total suspected cases reported this EW compared to that reported in the last EW. This method may not reflect the diagnoses that occurred during the past EW (some may have come from days or weeks earlier), but that level of detail is not available in the MOH report.

Confirmed and discarded M&CD diagnoses...

M&CD cases under investigation decreased by 130 to 3,580 this week - the sixth consecutive decrease. This may be occurring for a range of (guessed) reasons including:

  1. improved capacity to address a large volume of request for clinical classification of suspect diagnoses.
  2. streamlining the confirmation processes
  3. retrospective application of changed head circumference definitions resulting in reductions to the number of the microcephaly diagnoses.
    This aspect will not reduce the number of cases with structural brain changes that occur in the absence of a decreased head size - which are reportedly also related to Zika virus and/or other causal influences.
    There is time involved in making these diagnoses because of the need for detailed ultrasound and other diagnostic investigations to identify congenital infection outcomes including intracranial calcifications, dilation of cerebral ventricles or posterior fossa changes and other issues.

In the graph above, we can see that 172 (blue bars; right hand axis) suspected M&CD diagnoses were discarded upon closer investigation with a current total of 2,492 removed.

The rate of these resolved diagnoses (line with blue dots, left-hand axis) continues to outpace the rate of the smaller overall number of confirmed M&CD diagnoses (red dots, left-hand axis). 


As of this EW, 17% of suspected M&CD diagnoses have been confirmed while 34% of suspected diagnoses have been discarded. 


The cumulative number of M&CD diagnoses does continue its climb this EW, growing by 73 new diagnoses (red bars; right-hand axis) to total 1,271


The number of these M&CD diagnoses to be confirmed with a Zika virus infection also grows (green dots; left-hand axis) by 9 new detections to 203 this EW (green bars; right-hand axis). Those confirmed Zika virus infections represent 16% of all confirmed M&CD diagnoses and 3% of all suspect diagnoses - but these are not fair comparisons for a range of reasons I won't go on about here.


References...

  1. http://portalsaude.saude.gov.br/images/pdf/2016/maio/04/coes-microcefalia-informe-epi-24-se17-2016.pdf