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...

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

Are fewer Ebola virus disease cases being confirmed than previously?

A very quick graph plotting the proportion (percentage, %) of laboratory-confirmed Ebola virus disease (EVD) cases reported by the WHO over time. That is, the of samples taken from clinically suspected EVD cases that are RT-PCR positive for Ebola virus in a given report, divided by the total number of suspected + probable + confirmed cases in that report.

Taken from my static
EVD tallies and graphs
page here. Updated
28JAN2015 AEST.Click on graph to enlarge. 

Looking at the graph below, it seems like a lower proportion of total cases are being confirmed now compared to before the total case load began decreasing (especially from December onwards-see adjacent graphic). 

Presumably this is due to the larger number of other infectious diseases in the region that cause signs and symptoms, especially early signs and symptoms, that cannot be easily clinically differentiated from EVD; more suspect cases that don't test positive for EVD than before.

When considered in the context of the now smaller number of EVD cases overall, the non-EVD infection's background "noise" has become louder.

But the bottom line is that EVD cases are steadily declining thanks to the many efforts of many people and the changes to habits, traditions and practices that increased risky contact.

The proportion (%) of EVD detection that are laboratory confirmed at each World Health Organization Situation Report or Situation Summary. Anomalous values have been removed. Click on graph to enlarge.

The control gap...

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MERS-CoV in the Netherlands...a detail analysis of cases

Red arrow indicates where Dutch 
MERS-CoV case sequences sit.
Click on tree to enlarge

This comes from a shiny newly released Eurosurveillance report from Dutch researchers. 

I've marked up my earlier tree to show where (based on partial 4,000nt fragment) the sequence from the Netherlands MERS-CoV positive cases (near identical) sits.

I've also charted Case 1's laboratory testing course, to show the variability of virus detection when a very thorough sampling and testing investigation is conducted. 

Viral RNA remained detectable in the blood for all days tested demonstrating viraemia (well, RNAaemia technically) from day-4 onwards. Urine was not positive but a faecal sample was, on day-5. The latter has implication for infection control in hospital settings whereby flushing toilets creating aerosols could be another contributor to spread.

Reverse transcription real-time polymerase chain reaction (RT-rtPCR) results are shown as positive (tall bars), negative (stumpy bars) or not tested (empty space) plotted against day of sampling.
Click on image to enlarge.

This is, as far as I'm aware, is only the second time human faeces or urine have been found to contain signs of MERS-CoV.

A throat swab was positive early on and then again after a 2-day period of negativity. This points to the possibility of shedding for over a week, when associated with cough. But given that this case was part of a tour group and they didn't all become symptomatic, MERS-CoV still didn't spread efficiently or result in disease very often (if it did spread), for whatever reason(s). Antibody testing would be interesting here too.

It would also be very interesting to know whether virus was being shed during the initial diarrhoea in Case 1, which predated his return to the Netherlands by about 8-days, or whether that was unrelated to the MERS-CoV infection. Perhaps testing faeces for gastrointestinal viruses would be useful, or interesting, here.

Ebola virus disease and lab testing...

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Influenza in Queensland, Australia...

Image adapted from Geoscience Australia,
The Australian Government.
http://www-a.ga.gov.au/web_temp/1531782/61756.pdf

Hot, humid and sunny are the conditions here just now. Although some rain around too-stormy rain with big dumps of water an flash flooding. Must be summer.

In the previous week's Queensland Health Statewide Communicable Disease Surveillance Report it looks as though we have a slight uptick in laboratory confirmed influenza cases so far this year (this is in total numbers, not proportions of samples tested, so take the value with a grain of NaCl) compared to the year-to-date totals for 2013 and 2012 in Queensland Australia.

As of the the 13-Jan update (data from 12.1.2014)

• 106 case notifications in 2014
• 73 cases by this time in 2013
• 41 cases by this time in 2012
• 144 cases by this time in 2011
• 21 cases by this time in 2010
• 12 cases by this time in 2009

More confirmation that rapid influenza diagnostic tests (RIDTs) should be used in context

The Texas Department of State Health Services have a useful couple of paragraphs from an Influenza Health Alert that puts into context reliance on the convenient and rapid, but ultimately intensive rapid influenza tests.

Rapid Lab Tests: Rapid Influenza Diagnostic Tests (RIDTs) can be useful to identify influenza virus infection, but false negative test results are common during influenza season. Clinicians should be aware that a negative RIDT result does NOT exclude a diagnosis of influenza in a patient with suspected influenza. When there is clinical suspicion of influenza and antiviral treatment is indicated, antiviral treatment should be started as soon as possible, even if the result of the RIDT is negative, without waiting for results of additional influenza testing.

Mike Coston also has an excellent article touching on some of the many other viruses that can cause influenza-like illness and on rapid testing, over on his blog, Avian Flu Diary. I highly recommend it.

Cost is always an important factor when hospitals and attached diagnostic laboratories consider how to address infections. Rapid turnaround time is another major cost because, for those small number of viruses with this option available, an antiviral drug can be administered and there seem to be benefits from doing this as early as possible for severe influenza. In some cases of course, a vaccine is available to block severe disease from occurring when you get infected (they don't stop infection, but a response to a vaccine is much safer than a bad response to an actual virus infection, as we've seen in the recent media for H1N1 in Texas. 

During flu season, influenza virus is an obvious cause for a spike in hospital admissions for acute respiratory symptoms - but if confirmation of that pathogen relies on a testing platform that can miss a third of infected individuals (only 17/45 PCR positives were detected by am RIDT in Ref#2) then antivirals may not be used in time. In a more recent comparison of RIDTs using PCR results as the standard, viral load in the upper airway (less virus gave fewer positives - duh), age (the young and elderly were less often positive), presentation time (sampling >2-days after onset of illness reduced the proportion of positivity), virus type (less sensitive for subtype B infections than A) and whether there was pneumonia or not (the former were less often positive perhaps reflecting less viral replication in the upper airway than in the lower airway?) were factors in how well the antibody-based RIDTs performed. Sensitivity ranged from 50% to 94%. These 2 studies used samples from the upper airways (swabs or nasopharyngeal aspirates respectively, as suggested by the BD™ Directigen EX Flu A+B assay, Alere™ Influenza A & B Test and the QuickVue® 117 Influenza A+B test)

In these instances, PCR-based methods (used as the "gold standard" in those published evaluations) shine but they take longer to generate a result and require more expertise to conduct than a rapid test. The slightly longer time is not just because they take hours to conduct instead of the minutes of a rapid test (remembering that viral lab diagnoses used to take days not hours) but because lab testing is only part of a process which also involves paperwork and passing verified and signed off results and information to all concerned clicnial parties and patients. That can take more time-and sometimes be a bottleneck for result release. Its hard for a patient's family and friends to wait, but the results will be that much more reliable when they come.

A feature of influenza season is the concurrently reduced levels of activity of other viruses. Influenza tends to "push out" a lot of other viruses during it's peak season - probably reflecting influenza's ability to dominate the immune response in an infected individual, and by extrapolation, reduces the number of susceptible individuals at the community level, remembering that the majority of influenza cases are acute upper respiratory tract illnesses.

So it looks more like the Montgomery County deaths may have been due to the high levels of influenza A(H1N1)pdm09 virus generally circulating in them there parts. A KHOU news outlet report, also circulated on ProMED, suggest that 4 Montgomery county deaths were due to H1N1, as well as other sine the regions. However, the Montgomery County Public Health District reports only 2 H1N1-confirmed deaths, so things are still a little confusing there. And as for whet other viruses may also be in these patients...so far, who knows?


A brief guide to some terms used in these sorts of discussions (also from Ref #2 below)

Sensitivity
No. of true positives / no of true positives and false negatives

Specificity
No. of true negatives / no of true negatives and false positives

Positive predictive value
No. of true positives / no of true positives plus no. of false positives

Negative predictive value
No. of true negatives/ no of true negatives


References and further reading...

1. FluTrackers story. http://www.flutrackers.com/forum/showthread.php?p=517368#post517368
2. Accuracy of rapid influenza diagnostic test and immunofluorescence assay compared to real time RT-PCR in children with influenza A(H1N1)pdm09 infection. http://www.ncbi.nlm.nih.gov/pubmed/23175329
3. Clinical and Virologic Factors Associated with Reduced Sensitivity of Rapid Influenza Diagnostic Tests in Hospitalized Elderly and Young Children. http://www.ncbi.nlm.nih.gov/pubmed/24285739

Are H7N9 case contacts being tested or just observed?

No epidemic linkage found between any of the H7N9 cases to date, and no "abnormality" among any of 621 close contacts. 

Sounds like contacts are not being subjected to laboratory testing.