Wednesday, 27 July 2016

Public Zika virus data can be volatile Zika virus data...

So it turns out I hadn't had a stroke or started losing my mind. 

....10 hours earlier....

I received an answer to my questions tweeted at the Colombian National Institute of Health asking why Colombia's Zika virus (ZIKV) data had been revised downward. Was it simply data cleaning? How did it happen? Why now? As you can see from the drop in weekly figures (that last red bar), it was a quite a cleanup if so - a drop in 5,000 cases!
Graph No. 1. 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) including the original
epidemiological week No. 28 data. Data from [1].
Click on graph to enlarge.

Graph No.2. 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) including the original 
epidemiological week No. 28 data. 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.










































Dr Fernando Ruiz, the Deputy Minister of Public Health and Service Delivery Colombia kindly engaged me on Twitter, telling me that each week their data get adjusted to account for current and former week's lags. I sent him Graph 1 above to try and reiterate that this past epidemiological week had been a bit different than any other this year. When he bounced some numbers at me something seemed weird - these were different from what I'd recorded. 

Sure enough, my spreadsheet no longer matched up with the numbers I'd harvested on Sunday morning (my time, AEST) from the Week No.28 Colombian Epidemiological Bulletin.

Weird. My usual first reaction - it's all my fault. Had I been daydreaming when I copied the numbers across? Had my Excel formulae betrayed me (never!)? Had the kids edited my blog? Had the cat sneakily deleted and typed a few figures. Had I had a small cerebral incident? Am I having one now?

Am I doomed to never know the answer?

Thankfully, @FluTrackers had a post from @thelonevirologi including charts and numbers from the Colombian data and sure enough a key figure was there that was common to both our datasets - but no longer anywhere to be found on the Colombian bulletin - 7 166 confirmed laboratory cases. And, coming to the rescue of my sanity, @thelonevirologi still had the original PDF - the data had indeed been released wrongly and then corrected and re-released by the National Institute of Health. Phew.

Public data are volatile

This really is a stark reminder that public data are volatile and can change. 

Sometimes that change may not be identified by the publisher - no version numbering and no note to say what changed and why. Simple stuff to add, but sometimes completely absent. 

We bloggers, who live in the 'grey literature' world (and rarely attract citations from the scientific literature), may be better at understanding the need to own our changes and mistakes. We often try to correct them in a way that is obvious to those who use or even rely on our information. This is just good practice.

And what about Colombia's ZIKV numbers this week?

As to the updated ZIKV figures from Colombia, the revised versions show that clinically suspect ZIKV disease cases do in fact continue to rise (+933) and that there were 22 more confirmed cases among pregnant women added this past week. No general ZIKV disease confirmations were reported after the 176 from last week and no new cases of ZIKV-associated microcephaly were added this week after 4 consecutive weeks of growth. Perhaps this is one of those laboratory 'off weeks'.

Colombia notes that it expects ZIKV-related microcephaly cases to increase in September and October 2016 as more pregnant women come to term.[2] A nearly 8% increase in (known) miscarriages has already been reported in Colombia but no rise in the use of abortion clinics which might otherwise "hide" the congenital impact of ZIKV infection not registered as microcephaly.[3] 

Given these ZIKV infections are still being suspected and detected, it seems very strange that Colombia picked now to declare it's epidemic over.[2] For certain, numbers have been slowing each week for at least 6 weeks but they are still being reported (perhaps just lagging older results?). 

A quick summary: sexual events play a role in ZIKV transmission, persistence of virus is real at several sites, we have not yet examined all possible transmission avenues (oral and respiratory epithelium, eyes, ingestion) and we still don't know whether the 80% of cases that are asymptomatic play any role in human-to-mosquito or human-to-human transmission nor whether that 80% figure still holds today. 

Perhaps the Colombians simply mean that the ZIKV numbers per week have fallen below some arbitrary internal epidemic threshold value now. Maybe cases are still being identified, just not at epidemic levels or rates. I'd have thought a threshold would take more than a year and a bit to determine for a new disease with so much still unknown, but perhaps not.

Graph No. 3. The corrected 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) including the updated
epidemiological week No. 28 data. Data from [1].
Click on graph to enlarge.



 
Graph No.4. 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) including the updated
epidemiological week No. 28 data. 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.

References...
  1. http://www.ins.gov.co/boletin-epidemiologico/Boletn%20Epidemiolgico/Forms/public.aspx
  2. http://www.nytimes.com/2016/07/26/world/americas/colombia-zika-epidemic-end.html?partner=rss&emc=rss&smid=tw-nytimes&smtyp=cur&_r=0
  3. https://www.washingtonpost.com/world/the_americas/colombia-offers-the-possibility-that-the-zika-epidemic-may-not-be-as-bad-as-feared/2016/07/12/d8c91e60-3d78-11e6-9e16-4cf01a41decb_story.html?postshare=8051469159730881&tid=ss_tw


Sunday, 17 July 2016

Colombia Zika virus report, Epidemiological Week No. 27...

The latest epidemiological report from Colombia, which includes data on Zika virus disease (ZVD; 03JUL2016-09JUL2016), 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 176 new laboratory confirmed cases of ZVD were reported this week. The total sits at 8,826 or 10% (the highest proportion reported to date-steady for the  past 6 reporting weeks) 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 in a linear fashion, adding 984 this week to total 89,962.


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 (EW) No. 27, 11,614 suspected (+77 compared to last week) and 5,882 confirmed ZIKV infections (+135) have been identified in pregnant women.

As of this report, 21 (+3 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 0.36% of all confirmed ZIKV positive mothers-the 4th EW in which this proportion has risen.

Some back of napkin calculations looking at these numbers suggest that there are 3-4 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.

160  other microcephaly diagnoses (up from 112 last week and the highest value to date) 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. 
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 275 days, or 9 months 1 day, since ZIKV was first confirmed in Colombia on 16th October 2015.[2] Colombia is currently carrying the next biggest load of ZVD 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 (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...

Wednesday, 6 July 2016

Kids are virus factories...

UPDATE #1: 06JUL2016
Ms. Mohinder Sarna and Associate Professor Lambert have just recently published some cool data from a large and very heavily sampled respiratory virus-related study.

The new report comes from a large birth cohort study entitled the Observational Research in Childhood Infectious Diseases (ORChID) study. 

ORChID is a "longitudinal community-based dynamic birth cohort study of ARI [acute respiratory infection] episodes in children from birth to 2 years of age in the subtropical city of Brisbane, Australia". The study followed babies until they were two years old, taking weekly - yes, WEEKLY! - respiratory swabs and dirty nappy swabs and then tested the heck out of them for known viruses and bacteria. 

The testing results are not part of this report so use of the term "infection" is presumptive. For this study I would have preferred ARI=acute respiratory illness; URTI-upper respiratory tract illness; LRTI-lower respiratory tract illness. But infection is being used in the sense of the clinical picture, where a long history of literature and prior knowledge informs a medical doctor's definition of these acute illnesses as most likley due to virus infection

The details of the study's intentions were previously spelt out in Observational Research in Childhood Infectious Diseases (ORChID): a dynamic birth cohort study.[1]

But the topic of this post is the latest publication from this cohort study: The Burden of Community-Managed Acute Respiratory Infections in the First 2-Years of Life.[2; unfortunately it's paywalled but abstract is visible]. 

I'm not reviewing the whole thing today, I just wanted to pick out a couple of bits and a figure because it really exemplifies how often our little darlings become ill. These are generally mild illnesses and usually without any long term problems. Of course, that doesn't make the grown-ups on the receiving of an infant with a very transmissible virus all that much happier!

A couple of interesting things:

  • this is a community rather than hospital-based study which gives us a real snapshot of what happens in normal life - interpret that with the knowledge that infants were "from families of more advantaged backgrounds, which is common in longitudinal cohort studies"
  • otherwise healthy infants in this cohort had a distinct illness every 2 months on average; fewer during the first 6 or so months but more after that 
  • sampling density is phenomenal - weekly samples. Also a good participant retention rate and 78% of expected days were captured
  • antibiotics were prescribed in 21.9% of all ARI episodes - usually for acute otitis media (middle ear infection), and more often for a LRTI than an URTI
  • when antibiotics were prescribed for upper respiratory tract illnesses (well known to be overwhelmingly viral in nature and this not targeted by an antibacterial drug), it was most often in family physician visit older male doctors
    Note: Table 4 in the paper should not have had "Antibiotics" indented-personal communication with thanks to A/Prof Lambert for clarifying
  • some minor illness may have been missed because symptoms including fever, mood change and poor feeding are hard to measure in this very young age group.
    "I say mother, I'm feeling a tad peaked this morning". Umm, no. More like "Waaah!"


Copyright © 1999-2016 John Wiley & Sons, Inc. All Rights Reserved.
Publication: Pediatric Pulmonology; Content Title: The burden of
community-managed acute respiratory infections in the first 2-years of life;
Content authors: Mohinder Sarna,Robert S. Ware,Theo P. Sloots,
Michael D. Nissen, Keith Grimwood,Stephen B. Lambert.[2]
Reprinted with permission granted by Dr Sarna and RightsLink. License No. 3902730655132. 
Click on image to enlarge.
It will also be really interesting to see how often these children are infected but without a measurable illness resulting. 

What will the total number of infections look like in a year, in the community, among young children? More than a single infection every 2 months is my (highly biased) bet. That paper is coming, but unlike winter, it is not yet here.

Disclosure...

I have also been a little involved with this study during my previous life, as acknowledged elsewhere.[1]

References...
  1. Observational Research in Childhood Infectious Diseases (ORChID): a dynamic birth cohort study.
    http://bmjopen.bmj.com/content/2/6/e002134.long
  2. The Burden of Community-Managed Acute Respiratory Infections in the First 2-Years of Life.
    http://onlinelibrary.wiley.com/doi/10.1002/ppul.23480/abstract
Updates...
  1. Author title changes

Tuesday, 5 July 2016

Brazil's microcephaly and CNS disorder (M&CD) monitoring: Report No. 32, 2016-Week No. 25...

These graphs are made by me using data obtained from epidemiological week (EW) number 25'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 confirmed.[2,3]

Suspected M&CD cases...

The total number of suspected M&CD cases increased by 126 to 8,165 this EW (compared to last).



The graph above shows the number of suspected M&CD diagnoses in Brazil up to 25-June-2016. The cumulative curve (yellow dots; left hand axis) is growing, but slowly. 

This was another 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 increased by 54 to 3,061 this week.


In the graph above, we can see that 50 (blue bars; right hand axis) suspected M&CD diagnoses were discarded upon closer investigation with a current total of 3,466 removed.

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

As of this EW, 20% of suspected M&CD diagnoses have been confirmed while 42% of suspected diagnoses have been discarded-a percentage that has been steady for 4 EWs.

The cumulative number of confirmed M&CD diagnoses does continue its climb this EW, growing by 22 new diagnoses (red bars; right-hand axis) to total 1,638.


The number of these M&CD diagnoses to be confirmed with a Zika virus infection also grows (green dots; left-hand axis) by 37 new detection (green bars; right-hand axis) to 270 this EW after rising by 7 the preceding EW.

Those confirmed Zika virus infections represent 16% (an increase for the first time about 11 weeks) of all confirmed M&CD diagnoses and 3% of all suspect diagnoses.

References...

  1. http://portalsaude.saude.gov.br/images/pdf/2016/junho/30/Informe-Epidemiol--gico-n---32--SE-25-2016--27jun2016-16h18.pdf
  2. http://combateaedes.saude.gov.br/images/sala-de-situacao/informe_microcefalia_epidemiologico26.pdf
  3. http://combateaedes.saude.gov.br/images/boletins-epidemiologicos/2016-013-Dengue-SE16.pdf

Sunday, 19 June 2016

Colombia Zika virus report, Epidemiological Week No. 23...

The latest epidemiological report from Colombia, which includes data on Zika virus disease (ZVD; 05JUN2016-11JUN2016), has been produced by the Colombian National Institute for Health team.[1]
NOTE: While these data are from those 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 zero new laboratory confirmed cases of ZVD were reported this week-this must be an "off" week for laboratory reporting - you can see others in the above graph where the green bars sit at zero. The total still rests at 8,221 or 10% (the highest proportion reported to date) 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 in a linear fashion, adding 2,086 this week to total 85,021
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. 23, 10,704 suspected (+268 compared to last week) and still 5,420 confirmed ZIKV infections (+zero-no lab results this week) have been identified in pregnant women.

As of this report, 6 (+0 from last 2 weeks) live births have been diagnosed with microcephaly/central nervous system disorders and were reported as being ZIKV positive; 81 (up from 69 last week and the highest value to date - could things be picking up pace?) other microcephaly diagnoses are now under investigation.[1] That represents 0.11% of all confirmed ZIKV positive mothers. 

Graph No. 4 below focuses on just these ZIKV-positive cases and those that remain under investigation, highlighting how the investigatory total has changed each week, but has also been trending upwards since Epidemiological Week No. 14. This may be a marker of a rise in microcephaly and other congenital disorders.
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 247 days, or 8 months 3 days, 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 (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 different from Brazil.[5]

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]

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:

  1. The time taken for health care centre ZIKV disease (ZVD) data to be reported by the INS is approximately 1.5 weeks
  2. 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
  3. 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 
  4. 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
  5. 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.
  6. 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
  7. No antibody testing was available - that means a lot of missed opportunities to confirm suspect ZVD diagnoses
  8. 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
  9. 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
  10. 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
  11. 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 
  12. 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
  13. 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...


  1. http://www.nejm.org/doi/pdf/10.1056/NEJMoa1604037
  2. http://wwwnc.cdc.gov/eid/article/14/8/08-0287_article
  3. http://www.nejm.org/doi/pdf/10.1056/NEJMoa1602412
  4. https://www.statnews.com/2016/06/14/zika-olympics-who/
  5. http://virologydownunder.blogspot.com.au/2016/06/colombia-zika-virus-report_12.html
  6. http://www.neurology.org/content/73/11/887.full.pdf+html

Sunday, 12 June 2016

Colombia Zika virus report, Epidemiological Week No. 22...

The latest epidemiological report, which includes data on Zika virus disease (ZVD; 22MAY2016-04JUN2016), has been produced by the Colombian National Institute for Health team.[1]
NOTE: While these data are from those 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 639 more laboratory confirmed cases of ZVD were reported this week than last. The total now rests at 8,221 or 10% (the highest proportion reported to date) 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 in a linear fashion, adding 1,572 this week to total 82,935
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. 22, 10,436 suspected (+17 compared to last week) and 5,420 confirmed ZIKV infections (+529) have been identified in pregnant women.

As of this report, 6 (+0 from last week) live births have been diagnosed with microcephaly/central nervous system disorders and were reported as being ZIKV positive; 69 (up from 48 last week) other microcephaly diagnoses are now under investigation.[1] That represents 0.11% of all confirmed ZIKV positive mothers (as drop from last week). Graph No. 4 below focuses on just these positive cases.
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 239 days, or 7 months 26 days, 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 (probably-still not definitive). 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]

Saturday, 11 June 2016

More microcephaly to come..?

The Brazilian Ministry of Health presented some information around Zika virus (ZIKV), June 10. Specifically some good news about its recent steady decline ahead of the Olympics. Good timing, huh?

Its always good to see some data - it's unclear if these are clinically suspected (most probably) or laboratory confirmed cases (highly unlikely given the numbers being so high and lab capacity being reportedly so low) from this graph, but if we look further down at Figure 2, the Pan American Health Organization data, which lists slightly fewer cases each week that Brazil (PAHO figures may need updating?), does not list any confirmed cases, only "suspected". I assume that means rashy febrile people. 

If we add up the weeks listed by the Ministry, there have been 159,914 cases in 2016.

Figure 1. From Brazil Ministry of Health slideset, June 10.
Slides No.12 and No. 13 [1]
Click on image to enlarge.
So, if these are ZIKV and not Dengue virus, Chikungunya virus, an enterovirus or some other acute cause of rash [2], then should we expect to see a new wave microcephaly and central nervous system disorders starting from around July? I've said July because that is about 184 days pr 6 months after the rise starts - 184 being the magic number between when ZIKV was first identified in Brazil (although we are pretty sure it was there much earlier[3]) and when the first 141 microcephaly diagnoses were announced.[4]

Meanwhile, Colombia - the elephant that won't leave the room - reports just 6 ZIKV-linked microcephaly diagnoses despite nearly eight months having passed since they first identified local spread of ZIKV and there already being nearly 5,000 pregnant women confirmed as ZIKV infected.[5] 

Brazil reports just 3,598 pregnant women clinically, epidemiologically or laboratory (presumably a much smaller number) confirmed as infected with ZIKV yet its population is a quarter of Brazil's (48 versus 200 million according to 2013 data via Google). It's a strange one that could be explained by ZIKV alone not being the cause of microcephaly or else by those extra years during which ZIKV was in Brazil but not yet Colombia being somehow key to the occurrence of microcephaly. 

First we need a little more genome sequencing to understand whether ZIKV was also present in Colombia for longer than dictated by its first laboratory confirmed case report. Perhaps a ZiCRA project is required?[5]

Meanwhile, it would be great if Brazil published its national numbers in a weekly report - along with confirmed numbers. The promise of the "Boletins Epidemiol√≥gicos de Dengue, Chikungunya e Zika" has not been realised with only two reports over the past 10 epidemiological weeks and no specific listing of laboratory confirmed numbers.[6] 

I can't help but recall that some were very upset at The Kingdom of Saudi Arabia for what was, in hindsight, relatively better epidemiology data for MERS-CoV. Strange why this has not been an issue here. One of the many mysteries of Zikasteria? I have no answer. 

References...

  1. http://portalsaude.saude.gov.br/images/pdf/2016/junho/10/saude-nos-jogos-olimpicos-e-paralimpicos.pdf
  2. http://virologydownunder.blogspot.com.au/2016/01/zika-virus-briefly.html
  3. http://science.sciencemag.org/content/early/2016/03/23/science.aaf5036.full
  4. http://virologydownunder.blogspot.com.au/search?q=184
  5. http://zibraproject.github.io/about/
  6. http://combateaedes.saude.gov.br/situacao-epidemiologica#boletins

Brazil's microcephaly and CNS disorder (M&CD) monitoring: Report No. 29, 2016-Week No. 22...

These graphs are made by me using data obtained from epidemiological week (EW) number 22'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 confirmed.[2,3]

Suspected M&CD cases...

The total number of suspected M&CD cases increased by 107 to 7,830 this EW (compared to last).


The graph above shows the number of suspected M&CD diagnoses in Brazil up to 04-June-2016. The cumulative curve (yellow dots; left hand axis) is growing, but slowly.

This was another 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 145 to 3,017 this week - the eleventh consecutive decrease.



In the graph above, we can see that 190 (blue bars; right hand axis) suspected M&CD diagnoses were discarded upon closer investigation with a current total of 3,262 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, 20% of suspected M&CD diagnoses have been confirmed while 42% of suspected diagnoses have been discarded-a percentage that has increased for 18 weeks.

The cumulative number of confirmed M&CD diagnoses does continue its climb this EW, growing by 62 new diagnoses (red bars; right-hand axis) to total 1,551.


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 224 this EW after rising by 15 the preceding EW.

Those confirmed Zika virus infections represent 14% of all confirmed M&CD diagnoses and 3% of all suspect diagnoses.


References...

Sunday, 5 June 2016

Colombia Zika virus report, Epidemiological Week No. 21...

The latest epidemiological report, which includes data on Zika virus disease (ZVD; 22MAY2016-28MAY2016), has been produced by the Colombian National Institute for Health team.[1]
NOTE: While these data are from those 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 1,180 more laboratory confirmed cases of ZVD were reported this week than last. That's a big rise but follows a zero addition week last week. The total now rests at 7,582 or 9% (reaching the highest proportion reported to date) 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 in a linear fashion, adding 4,096 this week to total 81,363 suspected cases of ZVD. This is the biggest weekly rise since Week No.8.
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. 21, 10,419 suspected (-735 compared to last week - the biggest negative adjustment on record) and 4,891 confirmed ZIKV infections (+794 - 2nd biggest weekly rise to date) have been identified in pregnant women.

As of this report, 6 (+1 from last week) live births have been diagnosed with microcephaly/central nervous system disorders and were reported as being ZIKV positive; 48 (down from 57 last week) other microcephaly diagnoses are now under investigation.[1] That represents 0.12% of all confirmed ZIKV positive mothers (same value for past 3 weeks). 
Graph No. 4 below focuses on just these positive cases.
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 232 days, or 7 months 19 days, 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 (probably-still not definitive). 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]