Non-Invasive Dengue Diagnostics-The Use of Saliva and Urine for Different Stages of the Illness.

Mahathir Humaidi,Wei Ping Tien,Grace Yap,Lee Ching Ng,Choon Rong Chua

doi:10.3390/diagnostics11081345

Mahathir Humaidi, Wei Ping Tien + Show 3 more

Open Access

https://doi.org/10.3390/diagnostics11081345

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Abstract

Dengue diagnosis is largely dependent on clinical symptoms and routinely confirmed with laboratory detection of dengue virus in patient serum samples collected via phlebotomy. This presents a challenge to patients not amenable to venipuncture. Non-invasive methods of dengue diagnosis have the potential to enhance the current dengue detection algorithm. In this study, samples from dengue infected patients were collected between January 2012 until September 2012 and September 2013 until December 2013 in two different setups. Panel A samples (blood, urine, and saliva) were collected daily when the 39 patients were hospitalised and during their follow-up visits while Panel B samples (saliva) were collected from 23 patients during the acute stage of dengue. Using DENV PCR on Panel A, from day 2 to day 4 post fever onset, serum showed the best overall positivity followed by saliva and urine (100%/82.1%/67.9%). From day 5 until day 10 post fever onset, serum and urine had similar positivity (67.4%/61.2%), followed by saliva (51.3%). Beyond day 10 post fever onset, DENV was undetectable in sera, but urine and saliva showed 56.8% and 28.6% positivity, respectively. DENV in urine was detectable up until 32 days post fever. Panel B results showed overall sensitivity of 32.4%/36% (RNA/NS1) for DENV detection in saliva. Our results suggest that the urine-based detection method is useful especially for late dengue detection, where DENV is undetected in sera but still detectable in urine. This provides a potential tool for the physician to pick up new cases in an area where there is ongoing dengue transmission and subsequently prompt for intensified vector control activities.

Highlights

Dengue is the world’s most common mosquito-borne virus, with approximately three billion people at risk of infection each year
We evaluated the performances of reverse transcriptase-polymerase chain reaction (RT-PCR) and DENV NS1 in saliva and urine samples collected from serum-based confirmed dengue patients in Singapore
All serotypes detected in urine and saliva matched those detected in the sera

Summary

Introduction

Dengue is the world’s most common mosquito-borne virus, with approximately three billion people at risk of infection each year. An accurate and quick laboratory diagnosis is essential for the clinician to distinguish initial-phase dengue from other diseases with similar clinical symptoms. Serologic assays of dengue-reactive IgM and IgG antibodies can be used to show if a patient has a primary or a secondary dengue infection. IgG is not suitable for early diagnosis of primary infection cases as it can be detected only after 10 days from illness onset. Rapid increase of IgG can be detected from as early as day 4 after illness onset [11]. Dengue IgA has been detected in serum of febrile patients between days 8 and 11 after fever onset of a primary dengue infection. IgA increases almost immediately after fever onset [12,13]

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