## 3 Technical and Pre-Analytical Considerations
panels are adenovirus 40/41, astrovirus, norovirus genogroup I/II, rotavirus A, and, in some assays, sapovirus. These pathogens represent the most important viral causes of AGE (Table 3). Before the introduction of a novel diagnostic technique, the analytical sensitivity or the limit of detection needs to be known for every target. Comparison studies of current syndromic panels have demonstrated equivalent or even superior performance to reference assays [45, 48, 49]. Not surprisingly, performance data varied between panels but also within panels with respect to specific pathogens [50, 51]. Frequently, overall sensitivity is shown but might be critically low for selected targets [17]. In addition, genotypes can influence performance. For adenovirus, the most common types seen in AGE are included (types 40/41) in most assays. However, regionally circulating virus types might influence the reliability of results. Critically, validation studies conducted in tropical regions remain scarce but are of importance. Commercial panels include fixed combinations of pathogens and do not allow them to be customized, e.g., to local needs or seasonality of pathogens. It is well known that in temperate regions, norovirus and rotavirus typically occur in the colder month of the year (\"winter vomiting disease\"). In tropical regions, however, explosive outbreaks can occur with hundreds of cases due to the consumption of contaminated water irrespective of seasonality. On the contrary, selected pathogens may be rare overall, and consequently, the positive predictive value is very low. In addition, the introduction of the rotavirus vaccine also has an impact on the pretest probability and should be taken into account. Thus, knowledge about patients' vaccination status is of interest since rotavirus vaccination may also yield a positive PCR result for an indeterminate time period post vaccination [52]. In this respect, LDTs allow for greater flexibility as only locally relevant pathogens can be included. Finally, many available assays do have a CE label, which limits, e.g., the selection of the sample specimen type to those endorsed by the manufacturer. If alternative specimens are to be tested, extensive validation needs to be done to account for regulatory issues. \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Virus** & \begin{tabular}{c} **Mode of** \\ **Transmission** \\ \end{tabular} & **Target Population** & \begin{tabular}{c} **Incubation** \\ **Period (Days)** \\ \end{tabular} & **Clinical Significance** & **Vaccination** \\ \hline Sapovirus & \begin{tabular}{c} Fecal–oral; food \\ and water \\ \end{tabular} & \begin{tabular}{c} Infants and young \\ children; adults \\ less frequently \\ \end{tabular} & 1–2 & \begin{tabular}{c} Mild to moderate \\ gastroenteritis \\ \end{tabular} & No \\ \hline Rotavirus & \begin{tabular}{c} Fecal–oral; food \\ and water \\ \end{tabular} & \begin{tabular}{c} Infants and young \\ children; adults \\ less frequently \\ \end{tabular} & 1–2 & \begin{tabular}{c} Moderate to severe \\ gastroenteritis, including \\ severe dehydration; \\ hospital-acquired \\ infections occur \\ \end{tabular} & Yes \\ \hline Norovirus & \begin{tabular}{c} Fecal–oral; food and \\ water; possibly \\ via aerosols \\ \end{tabular} & All age groups & 1–2 & \begin{tabular}{c} Moderate to severe \\ gastroenteritis, including \\ hospital-acquired \\ infections; prolonged \\ shedding in \\ immunocompromised \\ patients \\ \end{tabular} & No \\ \hline Astrovirus & \begin{tabular}{c} Fecal–oral; food \\ and water \\ \end{tabular} & \
\begin{tabular}{c} Young children; adults \\ less frequently \\ \end{tabular} & 1–2 &
\begin{tabular}{c} Mild to moderate \\ gastroenteritis, including \\ asymptomatic infections \\ \end{tabular} & No \\ \hline \hline \end{tabular}
\end{table} 
Table 3: Baseline characteristics of frequently included pathogens in multiplex PCR panels. One of the most promising benefits of the new syndromic cartridge-based panels is the reduced hands-on and turn-around time.