Abstract
Norovirus (NV) is an important cause of acute gastroenteritis in children, but is also frequently detected in asymptomatic children, which complicates the interpretation of NV detection results in both the clinical setting and population prevalence studies. A total of 807 faecal samples from children aged <5 years hospitalized for acute gastroenteritis were collected in Thai Binh, Vietnam, from January 2011 to September 2012. Real-time RT-PCR was used to detect and quantify NV-RNA in clinical samples. A bimodal distribution of cycle threshold (Ct) values was observed in which the lower peak was assumed to represent cases for which NV was the causal agent of diarrhoea, whereas the higher peak was assumed to represent cases involving an alternative pathogen other than NV. Under these assumptions, we applied finite-mixture modelling to estimate a threshold of Ct <21·36 (95% confidence interval 20·29-22·46) to distinguish NV-positive patients for which NV was the likely cause of diarrhoea. We evaluated the validity of the threshold through comparisons with NV antigen ELISA results, and comparisons of Ct values in patients co-infected with rotavirus. We conclude that the use of an appropriate cut-off value in the interpretation of NV real-time RT-PCR results may improve differential diagnosis of enteric infections, and could contribute to improved estimates of the burden of NV disease.
Highlights
Detection sensitivities depend on many factors such as sample preparation methods, RNA extraction, presence of reverse-transcriptase inhibitors, primer design, amplification chemistries, virus concentrations in the sample, as well as viral factors such as genetic variation in circulating strains
We modelled the NV cycle threshold (Ct) value bimodal distribution with a finite-mixture model, which allowed us to identify a Ct threshold value associated with disease risk
In Thai Binh Paediatric hospital, 89% and 97% of children hospitalized for diarrhoea were aged less than 24 and 36 months, respectively (Table 1)
Summary
Norovirus (NV) (family Caliciviridae, genus Norovirus) is a major cause of gastrointestinal disease worldwide, and the cause of an estimated 200 000 deaths and 1·1 million hospitalizations in children. The NV detection rate in diarrhoeal patients varies from as high as 31–48% [3,4,5] to as low as 3–5% [6], suggesting that the burden of NV disease may be highly variable geographically. NV diarrhoeal patients are known to shed virus for prolonged periods of time following recovery [20]
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