Sunday, 3 April 2016

Usefulness of urine samples for Zika virus testing...

There is a narrow window of Zika virus (ZIKV) detectability in the blood (viraemia) based on the RT-PCR testing of serum samples from symptomatic cases. I've talked a little about this in a smaller, earlier post: Zika virus disease samples...don't pass urine (by)..

Little is known about asymptomatic infections and viraemia.

A decent number of studies have shown that urine may be a better sample for testing using molecular methods because of prolonged viral shedding (viruria) and sometimes higher viral load compared to serum samples.

The following is a list of some of the peer-reviewed literature and some public health advisories that have mentioned seeking ZIKV in urine using molecular techniques.


Australian Department of Health
Blood & Urine: 1st 14 days post symptom onset
http://www.health.gov.au/internet/main/publishing.nsf/Content/ohp-zika-health-practitioners.htm#toc05

European CDC
Blood: 3-5d post onset
Urine: up 10 10d

Public Health England
Blood: Anyone with travel history and current/past symptoms suggetsing ZIKV infection
Urine: Pregnant woman with current symptoms/male with current symptoms and a pregnant partner
https://www.gov.uk/guidance/zika-virus-sample-testing-advice 

United States CDC
Serum\CSF: Must be collected as primary test substrate
Urine: Can also be submitted
                                     
Kutsuna et al
In 1/2 cases, ZIKV RNA detected in urine when serum negative

Gourinat et al
Detected in urine of 6/6 symptomatic patients between 10 to 20 days after onset (7-20d better than serum), often with higher viral loads from urine samples than from serum. Serum positive in 4/6 but only until rash observed (2-3d post onset). Urine levels rise slightly after disease and rash onset - “preferred for virus detection”.



Shinohara et al
ZIKV RNA detected in urine 7 days after symptom onset; serum equivocal at 2 days post-onset

Besnard et al
Urine positive in 2 cases up to 8 days post-onset, in one case after serum was negative

Brasil et al
Of 88 women, 72 (82%) had positive results for ZIKV on PCR in blood, urine, or both; 60 in serum specimens; 46 in urine samples; 34 in both specimens; 12 in urine specimens only; 26 in blood specimens only; median number of PCR cycles for serum specimens - 33.0; median number of PCR cycles for urine specimens - 29.0.

Roze et al
Urine positive in 2/2 cases when serum was negative. 15-21 days after neurological symptom onset.

Barzon et al
Urine and had 106-fold higher viral loads than serum. Both sample types positive from 5 days after symptom onset, Urine positive until 22 days after onset-saliva until 29 days.


The outcome here is that urine is a sample that looks like it should be requested perhaps much more often than it is. Also, the language around recommending the collecting of urine is not as clear as it appears that it should be - including by some other public health agencies 

As it stands, a negative serum RT-PCR test for ZIKV does not hold a lot of meaning because of the narrow detection window using blood. 

Urine has proven itself useful for detection and confirmation of ZIKV infection - a process that is key to learning more about the virus and its impact(s) on infected humans. 

Use urine. Welcome the wee. Take the...well you get the point.