Active substances: Ciprofloxacin
While nurses provided necessary fluids to prevent dehydration, the study physicians decided that none of the volunteers required rehydration with oral rehydration salts solution or with intravenous fluids.
ETEC was detected in stool specimens of all volunteers prior to ciprofloxacin treatment.
Most symptoms were grade-1 and 2, none of the volunteers had grade-4 or -5 symptoms, but two volunteers had grade-3 abdominal pain, 1 had grade-3 abdominal cramps, and one had grade-3 bloating.
There were seven cases with fever all grade-1, and six with chills 5 grade-1 and 1 grade-2, but no case with signs of hypovolemia.
No severe adverse events were observed. On day 7, 10 and 28 after challenge, the corresponding IgA antibody levels were 136. All but one participant exhibited at least a two-fold response to the challenge strain.
The geometric mean fold increase in the IgA level from day 0 to day 7, 10, and 28 was 10. Serum IgA antibody levels against live TW 10598 bacteria measured as arbitrary units AU by flow cytometry in 30 adult volunteers at different time points, pre day 0 and post experimental infection.
First, as there is a lack of sites that are capable of performing large experimental infection studies, including Phase IIB trials, and, to the best of our knowledge, no facility for such studies in Scandinavia, we aimed at establishing such capacity at HUH.
We undertook the study in the hospital in a way that was compatible with everyday work in the ID ward, and the method should be subsequently applicable in similar institutions elsewhere.
The second aim was to develop a new challenge model for ETEC, involving an epidemiologically relevant strain. The present work describes the methods used to establish competence and capacity to perform experimental infection with ETEC within our hospital.
HUH is co-located with the University of Bergen, and, in our setting, we chose to approach students, many of them studying to become physicians.
We believe these students were likely to adequately comprehend all information required to refuse or provide a genuinely informed consent, as well as follow the study procedures.
As HUH has a restricted number of beds under isolation, we had to rely on inclusion of a few individuals at a time. This was possible in our student population, as we could adjust their admission according to the availability of cohort isolation rooms.
Thus, volunteers were admitted primarily at times of low prevalence of communicable diseases, such as influenza, in our community.
The study team ensured volunteer safety by careful clinical monitoring similar to that presented in studies taking place in dedicated units and prompt treatment using procedures already established for care of patients with severe invasive and non-invasive infections.
The study principal investigator ABG is a senior intensive care specialist and responsible for the evaluation of the volunteers on a daily basis.