A randomized controlled trial to investigate safety and variability of egg excretion after repeated controlled human hookworm infection.J Infect Dis. 2020 Jul 10 [Online ahead of print]JI
Controlled human hookworm infections could significantly contribute to the development of a hookworm vaccine. However, current models are hampered by low and unstable egg output, reducing generalizability and increasing sample sizes. This study aims to investigate the safety, tolerability and egg output of repeated exposure to hookworm larvae.
Twenty-four healthy volunteers were randomized double blind to one, two or three doses of 50 Necatoramericanus L3 larvae at 2-week intervals. Volunteers were monitored weekly and were treated with albendazole at week 20.
There was no association between larval dose and number or severity of adverse events. Geomean egg loads stabilized at 697, 1668 and 1914 eggs per gram feces for the 1x50L3, 2x50L3 and 3x50L3 group respectively. Bayesian statistical modelling showed that egg count variability relative to the mean was reduced with a second infectious dose, however the third dose did not increase egg load or decrease variability. We therefore suggest 2x50L3 as an improved challenge dose. Model-based simulations indicates increased frequency of stool sampling optimizes power of hypothetical vaccine trials.
Repeated infection with hookworm larvae increased egg counts to levels comparable to the field and reduced relative variability in egg output without aggravating adverse events.