VDU's blog: ZVD

Showing posts with label ZVD. Show all posts

Sunday, 28 August 2016

Colombia Zika virus report, Epidemiological Week No. 33...

UPDATE No.1: 29AUG2016

The latest epidemiological report from Colombia, which includes data on Zika virus disease (ZVD; 14AUG2016-20AUG2016), has been produced by the Colombian National Institute for Health team.[1]
NOTE: While these data were reported the past epidemiological week, they may not be from that week. See earlier post about possible reporting lag.

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 0 new laboratory confirmed cases of ZVD were reported this week; the 6th week of this. The total sits at 8,826 or 9% of all clinically suspected 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 shows the change in suspected cases. These are not laboratory confirmed. The suspected ZVD cases continue to rise but have been slowing for weeks, adding 270 this week to total 93,551.

Graph No.3. The cumulative curve of clinically suspect (lilac triangles, left-hand axis) and 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 number 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 epidemiological week (EW) No. 33, 11,752 suspected (+30 compared to last week) and 6,054 confirmed ZIKV infections (-2) have been identified in pregnant women.

As of this report, 34 (+5 from last EW) live births have been diagnosed with congenital ZIKV syndrome (CZVS; microcephaly/central nervous system disorder), confirmed as being ZIKV positive. That represents 0.53% of all confirmed ZIKV positive mothers-the 4th consecutive EW in which this proportion has risen.

Some back of napkin calculations looking at these numbers suggest that there are 5-6 deliveries for every 1,000 ZIKV-positive pregnant women that result in a ZIKV infected baby with microcephaly. This assumes each neonate has been tested for ZIKV as [6] suggests. This figure has no clear understanding of the number of aborted or miscarried foetuses that are also occurring from ZIKV-positive pregnant women. Abortions and miscarriages will need a local baseline to understand the scope of this component of the impact of ZIKV infection.

209 other microcephaly diagnoses (down from 254 last week) are now under investigation - this value has also been rising very quickly and suggests suspicious CZVS cases in Colombia are accruing faster than the pace of complete investigation can keep up with.

It now seems very likely that we can expect those bars to keep rising steeply in the coming weeks. The line is well and truly crossed.

Graph No. 4 below focuses on just the ZIKV-positive cases and those that remain under investigation, highlighting how the investigatory total has changed each week and been trending upwards since Epidemiological Week No. 14 and rising by +5 for 2 weeks in a row.

Graph No.4. The change in confirmed ZIKV infection numbers
when detected in association with a microcephaly diagnosis, compared
to the preceding week's total (yellow bars, left-hand axis). Data are from [1].
Click on graph to enlarge.

It has now been 317 days, or 10 months 12 days, since ZIKV was first confirmed in Colombia on 16th October 2015.[2] Colombia is currently carrying the next biggest load of suspected ZVD cases [8] (although more confirmed in Puerto Rico. NB: not all of the "Casos confirmados" are lab confirmed, but I'm told most are).[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 (probably-still not definitive). The counts of virus occurring this week will have zero impact on what happened back then. Also keep in mind that Colombia may be reporting things differently from Brazil.[5,7]

Brazil first 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...

Updates...

Clarified Puerto Rico has more confirmed cases than Colombia but fewer suspected

Saturday, 18 June 2016

The elephant squeaked...

An interesting new paper came out from Pacheco and colleagues from Colombia's national institute of health (INS or Instituto Nacional de Salud) this week. The INS team have written up their Zika virus (ZIKV) data spanning from 9th August 2015 to 2nd April 2016.[1] ZIKV data were not being regularly collected prior to then.

For me, the main new outcome from this report is that there seem to be no adverse outcomes to babies born to mothers who were infected with symptoms suggestive of ZIKV infection, in the third trimester of their pregnancy. Phew.

I'm not surprised at the low number of ZIKV-related microcephaly diagnoses observed, because I've been following the INS's weekly reports on this which make that issue very clear. I talk a little more about that issue below.

There were quite a few other bits and pieces in this publication. I've tried to capture some of the ones I found interesting in the list below:

The time taken for health care centre ZIKV disease (ZVD) data to be reported by the INS is approximately 1.5 weeks
Elevations 2,000m above seal level are not considered a risk because they are above traditional ZIKV-mosquito habitats, but they may still harbour human cases that have travelled from lower elevations and these may be under-counted
In 2010, half (52%) of pregnancies in Colombia were unintended and condoms were used in the same proportion of sexual encounters reported by women. Any advice aimed at reducing risk of sexual transmission of ZIKV - or other sexually transmitted infectins - will need to innovate to get that message across
Two-thirds (67%) of suspected ZVD cases were reported in females. Incidence per 100,000 population was similar in children but higher in females. This may reflect more testing of, and concern among, women of child-bearing age
Most pregnancies with symptoms suggestive of ZVD were ongoing when this report came out. This supports the thinking that it is still too early to say that Colombia will not have the same ZVD-related congenital disease problems among its pregnant women that Brazil has claimedIn a subset of 1,850 pregnant women who delivered babies, 532 (29%; 16% of pregnancies were not ongoing-why was not made clear) experienced their symptoms in the first trimester, 702 (38%; 29% not ongoing) in the second and 616 (33%; 82% born at term with normal weigh; 2% at term but low weight, 8% preterm, 1% were perinatal deaths and 7% are ongoing) in the third.
Lanciotti primers were used for RT-PCR of serum samples, but they look to have been updated in this study. The names differ-1087 instead of 1086 in the cited publication by Lanciotti et al.[2], 1163 instead of 1162c, 1108-FAM instead of 1107-FAM.
It would be good to see what sequences were actually used here. Most RT-PCR testing (60% of 3,384 samples tested during this period) was on samples from pregnant women (see No. 4) and no testing of urine was discussed which is a shame because urine is reportedly a better sample for RT-PCR because the detection window can be extended beyond that of using serum alone
No antibody testing was available - that means a lot of missed opportunities to confirm suspect ZVD diagnoses
The INS mandates reporting of all symptomatic cases. I had a little hope that perhaps Colombia, because they have been good at reporting throughout this event, might have also looked at whether the "80% asymptomatic" figure from previous outbreaks still holds today. Okay - it was a teensy hope. It will need a specific study
Fever was an integral part of the INS case definition - but fever is absent in 20% to 72% of cases.[1,3] This could mean a lot of ZVD cases were not included in the analysis - with an unknown impact on linkage to microcephaly counts from Colombia
As STATNEWS reported earlier[4], the World Health Organization has indicated that Colombia is not reporting on aborted foetuses or miscarriages that might have been related to ZVD. The impact of this omission is unclear and it would be great to know more about the issues and concerns here
During this period 4 infants (born between weeks 37 and 39) were reported to have microcephaly and confirmed ZIKV infection; 1 had abnormal brain findings and 3 abnormal hearing evaluations and other findings were listed as well. However, none of the 4 mothers reported symptoms of ZVD during pregnancy. Colombia is capturing newborn issues other than head size, at least following that initial diagnosis of microcephaly being made
STORCH (syphilis, toxoplasmosis, other agents [which other?], rubella, cytomegalovirus, and herpes) screens, karyotype analysis and ZIKV virus testing of the subset of 1,850 pregnant women with suspected ZVD were the only other tests described.
Investigations into teratogenic or toxic causes of microcephaly [6] not happening - at least based on the contents of this report
Among 239 ZIKV-negative samples (another 316 were ZIKV positive-all collected within 7 days of symptom onset - 8 (3%) were positive for dengue virus and 23 (10%) for chikungunya virus

The authors conclude that women with symptoms suggesting ZVD in the 1st trimester, may start to deliver affected babies soon after the early April cut-off date that this report covers. It's now the second half of June though and we have only had 6 cases reported by Colombia.[5] This may all be because of those reporting differences and timing issues discussed above and elsewhere on VDU. We await some more discussion about precisely how that would be the case.

We should also remember that clinically suspected diagnoses in this neck of the woods can be fraught with difficulty because fever+rash can be caused by a very wide range of things - including other mosquito-borne viruses known to be co-circulating. Take those totals with a big grain of NaCl and look laboratory confirmed samples for trends. This is also bias because a lot of the Colombian laboratory focus has been on pregnant women.

Click to enlarge.

We really know very little about the incidence of ZIKV in the general population or about the proportion of confirmed ZIKV infections that have little or no disease or about the rate of microcephaly or other congenital disease outcomes from infection. These would be very useful numbers to have to help us understand different risks and they rely on an accurate denominator. By 'accurate' I mean one based on actual testing results, not one based on guesstimates and models that lean on "suspected" data. This knowledge gap equally applies across all of the epidemic countries though, not just to Colombia.

For now, the elephant in the room continues to be the subject of insufficient conversation.

References...

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 (ZIKV^BR) 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.

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
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
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)
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?
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?
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? ZIKV^BR and an African lineage ZIKV (ZIKV^AF) acted similarly.
In three dimensional cultures, neurospheres growing in the presence of 10 MOI of ZIKV^BR were smaller and cell death was apparent - the effect was not as strong with ZIKV^AF 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...

Friday, 29 April 2016

Brazil's microcephaly and CNS disorder (M&CD) monitoring: Report No. 23, 2016-Week No. 16...

These graphs are made using data obtained from Week 16's Brazil Ministry of Health microcephaly and foetal and infant microcephaly and central nervous system (CNS) disorders (M&CD) report [1] and media report.[2]

Suspected M&CD cases...

The total number of suspected M&CD cases increased by 78 to 7,228 this week - the smallest rise reported by Brazil to date. This should not be confused with comments in the latest World Health Organization's Zika virus (ZIKV) situation report which states...

"At this stage, based on the evidence available, WHO does not see an overall decline in the outbreak."

That statement refers to current data whereas Brazil's M&CD report #23 is describing events that may have occurred approximately 20 to 40 weeks ago.[3] I picked that range because foetal disorders with preceding ZIKV detection have been reported to occur very rapidly, between 17 and 20 weeks in one case study.[4]

The chart above reports the number of newly suspected M&CD diagnoses in Brazil up to 23-April-2016. The cumulative curve (yellow dots; left hand axis) is steady and growing, but slowly steadily. This was the lowest weekly rise (orange bars; right-hand axis) on record.

Confirmed and discarded M&CD diagnoses...

M&CD cases under investigation decreased by 31 to 3,710 this week - the fifth consecutive decrease.

In the graph above, we can see that 79 (blue bars; right hand axis) suspected M&CD diagnoses were discarded upon closer investigation.The rate of these resolved diagnoses (line with blue dots, left-hand axis) is slowing but still seems to be outpacing the rate of confirmed M&CD diagnoses (red dots, left-hand axis). The cumulative number of M&CD diagnoses does continue its climb this week (+30), but this is the smallest addition of new diagnoses on record (red bars; right-hand axis).

The number of these M&CD diagnoses to be confirmed with a ZIKV infection also grows (green dots; left-hand axis) but by just 2 new detections to 194 this week (green bars; right-hand axis). That's the smallest rise on record. Those confirmed ZIKV infections represent 16% of all confirmed diagnoses and 3% of all suspect M&CD cases - but these are not fair comparisons for a range of reasons I won't go on about here.

Why are M&CD diagnoses slowing...?

It's not precisely known why the numbers of M&CD diagnoses are slowing in Brazil. Whatever their cause(s), the trigger(s) for the anomalies occurred in the past - as far as 9 months or as close as perhaps 20 weeks. One suggestion which ties in with the timing of arbovirus epidemics in Brazil, is the weather and its impact on the mosquito breeding cycle. (Thanks Luis F. B. Correia) Mosquitoes are assumed to be the major vector for transmitting ZIKV, wherever in the world it may be. That's a safe bet as far as we know. Undoubtedly, reporting on mosquito detections is not a priority. Only Mexico has reported infected wild-caught mosquitoes to date.[5] There have been more monkeys identified as ZIKV-infected than mosquitoes![5,6] For now at least.

The rainy season begins in the north-east (where M&CD has mostly been diagnosed) in May. Infections are likely to pick up from then - if we crudely add 6-9 months to May 2015 we get to October-2015 - January-2016.

August saw a rise in microcephaly diagnoses in Pernambuco State in the north-east.[6]

November is when the Brazil ministry declared a link between M&CD and ZIKV.[7]

It all kinda fits.

None of these numbers are precise though because when and where ZIKV was becoming established in Brazil is not known. It is predicted to have been as early as May-December 2013 based on analysis of viral genome sequences to hand,[9] but local transmission was not detected (looked for?) until April/May 2015.[9,10] It may have been there earlier.

Solid data and answers continue to evade trapping. As do ZIKV positive mosquitoes apparently.

References...

Sunday, 24 April 2016

Colombia Zika virus report, Week No. 15...

The latest epidemiological report, which includes data on Zika virus disease (ZVD; 10APR2016-16APR2016), 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 zero new laboratory confirmed cases of ZVD reported this week. The total holds steady at 3,292 or 5% of all the clinically suspected Zika virus (ZIKV) detections. I wonder if this is further support for a theory that there is a lag in laboratory reporting in Colombia, or was there was no testing conducted (seems unlikely)?

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. Most of these are not laboratory confirmed, but (I'm presuming here) include those that were from Graph No. 1. The suspected ZVD cases keep accumulating - another 3,059.

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 Week No. 15, 11,099 suspected and 1,703 confirmed ZIKV infections have been identified in pregnant women. Last week there were 1,706 confirmed diagnoses so the purple bar for this week strays into negative territory (-3 compared to last week).

As of this report, 4 (increased by 2 from last week) live births have been diagnosed with microcephaly/central nervous system disorders and were reported as being ZIKV positive; 22 (up from 15) other microcephaly diagnoses are under investigation.[1]

References...

http://www.ins.gov.co/boletin-epidemiologico/Boletn%20Epidemiolgico/2016%20Boletin%20epidemiologico%20semana%2015.pdf

Sunday, 17 April 2016

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...

Tuesday, 12 April 2016

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...

Sunday, 10 April 2016

Colombia Zika virus report Week No. 13...

The latest epidemiological report, which includes data on Zika virus disease (ZVD; 27MAR2016-02APR2016), 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 big week to 02-APR-2016 with the addition of 458 new laboratory confirmed ZIKV detections.

It can't be known from these data, whether that is die to more testing, or a greater proportion of positives among those tested. There is not "total number of samples tested" denominator which can be used to gauge that.

Excised from Colombian NIH PDF.[1]

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.

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.

These are people with rash, fever, joint pain etc that look to doctors as though they have disease that could be due to infection by ZIKV. This is not a reliable way of diagnosing a specific disease when other viral and non-viral agents are known to be co-circulating that can also cause rash, fever etc. But when resources are low or stretched thin, clicnial diagnosis is what there is.

Interestingly, if you compare the patterns of green and red bar sizes - forgetting about actual values or missing data etc - the peak week for confirmed ZVD in Colombia, Week No. 8. was also the peak week for clinically suspected ZVD cases.

There was also a rise in both measures in Week No. 13. Clinical suspicion is not laboratory confirmation, but there seem to be some overlapping trends there.

In Guillain-Barre syndrome - it seems there has been a series of slightly decreasing diagnoses continuing in Week No. 13. Does that match up with the pattern of confirmed and suspected ZVD cases? Hard to tell but keep watching.

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). Data from [1].

Click on graph to enlarge.

Graph No. 3 shows that to Week No. 13, 10,261 suspected and 1,515 confirmed ZIKV infections have been identified in pregnant women. As of this report, 3 live births have been diagnosed with with microcephaly and were reported as being ZIKV positive; 30 other microcephaly diagnoses are under investigation.
But, it isn't clear to me if these 3 are to be added to the 7 infections reported here, or if these 3 are 3 of the 7 - the other 4 being reported in the next epidemiological week.

Thanks as ever to Colombia's NIH for providing nice data around which we can all have a think and a chat about patterns.

References...

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

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