Vaccine Preventable Disease Seroprevalence In a Nationwide Assessment of Timor-Leste (VASINA-TL) - study protocol for a population-representative cross-sectional serosurvey (preprint)

Introduction: Historic disruption in health infrastructure combined with data from a recent vaccine coverage survey suggests there are likely significant immunity gaps to vaccine preventable diseases and high risk of outbreaks in Timor-Leste. Community-based serological surveillance is an important tool to augment understanding of population-level immunity achieved through vaccine coverage and/or derived from prior infection. Methods and analysis: This national population-representative serosurvey will take a three-stage cluster sample and aims to include 5600 individuals above one year of age. Serum samples will be collected by phlebotomy and analysed for measles immunoglobulin G (IgG), rubella IgG, severe acute respiratory syndrome coronavirus-2 anti-spike protein IgG, hepatitis B surface antibody and hepatitis B core antigen using commercially available chemiluminescent immunoassays or enzyme-linked immunosorbent assays. In addition to crude prevalence estimates and to account for differences in Timor-Leste age structure, we will calculate stratified age-standardised prevalence estimates, using Asia in 2013 as the standard population. Additionally, this survey will derive a national asset of serum and dried blood spot samples which can be used for further investigation of infectious disease sero-epidemiology and/or validation of existing and novel serological assays for infectious diseases. Ethics and dissemination: Ethical approval has been obtained from the Research Ethics and Technical Committee of the Instituto Nacional da Saude,Timor-Leste and the Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research, Australia. Co-designing this study with Timor-Leste Ministry-of-Health and other relevant partner organisations will allow immediate translation of findings into public health policy (which may include changes to routine immunisation service delivery and/or plans for supplementary immunisation activities).

Antiviral metabolite 3'-Deoxy-3',4'-didehydro-cytidine is detectable in serum and identifies acute viral infections including COVID-19 (preprint)

There is a critical need for improved infectious disease diagnostics to enable rapid case identification in a viral pandemic and support targeted antimicrobial prescribing. Here we use high-resolution liquid chromatography coupled with mass spectrometry to compare the admission serum metabolome of patients attending hospital with a range of viral infections, including SARS-CoV-2, to those with bacterial infections, non-infected inflammatory conditions and healthy controls. We demonstrate for the first time that 3'-Deoxy-3',4'-didehydro-cytidine (ddhC), a free base of the only known human antiviral small molecule ddhC-triphosphate (ddhCTP), is detectable in serum. ddhC acts as an accurate biomarker for viral infections, generating an area under the receiver operating characteristic curve of 0.954 (95% confidence interval 0.923-0.986) when comparing viral to non-viral cases. Gene expression of viperin, the enzyme responsible for ddhCTP synthesis, is highly correlated with ddhC, providing a biological mechanism for its increase during viral infection. These findings underline a key future diagnostic role of ddhC in the context of pandemic preparedness and antimicrobial stewardship.