Misdiagnosis prevents accurate monitoring of transmission and burden for sub-critical pathogens: a case study of Plasmodium knowlesi malaria

Maintaining surveillance of emerging infectious diseases presents challenges for monitoring their transmission and burden. Incomplete observation of infections and imperfect diagnosis reduce the observed sizes of transmission chains relative to their true sizes. Previous studies have examined the effect of incomplete observation on estimates of pathogen transmission and burden. However, each study assumed that, if observed, each infection was correctly diagnosed. Here, I leveraged principles from branching process theory to examine how misdiagnosis could contribute to bias in estimates of transmission and burden for emerging infectious diseases. Using the zoonotic Plasmodium knowlesi malaria as a case study, I found that, even when assuming complete observation of infections, the number of misdiagnosed cases within a transmission chain for every correctly diagnosed case could range from 0 (0 - 4) when R0 was 0.1 to 86 (0 - 837) when R0 was 0.9. Data on transmission chain sizes obtained using an imperfect diagnostic could consistently lead to underestimates of R0, the basic reproduction number, and simulations revealed that such data on up to 1,000 observed transmission chains was not powered to detect changes in transmission. My results demonstrate that misdiagnosis may hinder effective monitoring of emerging infectious diseases and that sensitivity of diagnostics should be considered in evaluations of surveillance systems.