Biases in Attribution Methods for Norovirus and Rotavirus Diarrhea

BackgroundThe estimate of diarrhea burden attributed to a specific enteric pathogen--the population attributable fraction (PAF)--depends on the specific calculation method. Two conventional methods are commonly used to estimate the PAF for enteric infections: the "detection-as-etiology" (DE) method, which defines the PAF as the pathogen prevalence in diarrheal cases; and the "odds-ratio" (OR) method, which expresses the PAF as a function of the OR between pathogen detection and diarrhea. A third, less frequently used method uses the risk ratio (RR) to quantify the strength of infection. MethodsWe compared each conventional PAF (DE, OR, or RR PAF) to a model-based (MB) PAF, derived from a transmission model of enteric infection, and defined bias as the crude difference from this "true" MB PAF. We fitted the transmission model to site-specific qPCR data for norovirus and rotavirus detection from MAL-ED (an eight-country birth cohort studying enteric infections) and used the equilibrium states to calculate the MB PAF. ResultsFor both pathogens, the OR and RR biases were small at all sites (ranging from -5% to +3%), whereas the DE method consistently overestimated the PAF and its bias was the largest of the conventional methods. ConclusionsOur mechanistic model provides an independent alternative to conventional methods, quantifying pathogens-specific enteric burden and the biases in those methods. Our model suggests the DE PAF estimations are consistently biased, and validates the OR and RR methods as feasible, low-bias measures for quantifying enteric burden.