Speaker
Description
Giardiasis is usually treated successfully with short oral courses of nitroimidazoles or related agents, yet refractory infection remains clinically important and mechanistically under-modelled. We present a human within-host model for Giardia duodenalis motivated by a prolonged refractory infection in the presenting author, an epidemiologist. The model links trophozoite and cyst dynamics in the duodenum to oral treatment regimens, incorporating uncertain parasite growth, encystation, host clearance, and optional microbiome-mediated suppression. A central feature is explicit representation of duodenal drug exposure, rather than relying only on plasma pharmacokinetics, since orally administered drugs physically reach the proximal small intestine before systemic absorption. Parameters are informed by drug-label pharmacokinetics and published treatment-effectiveness estimates for metronidazole, tinidazole, albendazole, quinacrine, and combination regimens, with uncertainty propagated throughout calibration. The calibrated model is then used to examine whether prolonged or combination treatments are expected to reduce infection duration and treatment-failure risk, and to compare plausible mechanisms underlying acute versus chronic infection. More broadly, the study asks how much clinically observed refractory giardiasis can be explained by local exposure, within-host persistence, and uncertainty in treatment effect. Spoiler alert: the epidemiologist is cured.
