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]

References...

1. http://www.ins.gov.co/boletin-epidemiologico/Boletn%20Epidemiolgico/2016%20Bolet%C3%ADn%20epidemiol%C3%B3gico%20semana%2023.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/
5. http://virologydownunder.blogspot.com.au/2016/06/the-elephant-squeaked.html

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

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]

References...

1. http://www.ins.gov.co/boletin-epidemiologico/Boletn%20Epidemiolgico/2016%20Bolet%C3%ADn%20epidemiol%C3%B3gico%20semana%2022.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/

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 Epidemiológicos 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...

1. http://portalsaude.saude.gov.br/images/pdf/2016/junho/07/Informe-Epidemiol--gico-n---29--SE-22-2016--06jun2016-18h54.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

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]

References...

1. http://www.ins.gov.co/boletin-epidemiologico/Boletn%20Epidemiolgico/2016%20Bolet%C3%ADn%20epidemiol%C3%B3gico%20semana%2021.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/