Vibramycin

The study medication was doxycycline, brand name Vibramycin (Pfizer). A GMP-licensed pharmacy (Kantonsapotheke Zürich) manufactured, blinded, and randomized the study medication separately for males and females; mannitol was used as placebo. Randomization code was broken after the last participant completed the study, and after all data were checked for consistency. The study dose of 200 mg is the smallest antibiotic dose recommended by the manufacturer and the same dose that yielded a 60% reduction in threat memory consolidation in a previous report (Bach et al., 2018a (link)).

The study medication was the tetracycline antibiotic doxycycline, brand name Vibramycin (Pfizer). Study dose (200 mg) was based on a previous study using delay fear conditioning (Bach et al., 2019 (link)). Doxycycline demonstrably penetrates the blood-brain barrier (Mento et al., 1969 (link)) and is clinically used to treat neuroborreliosis (Dotevall and Hagberg, 1989 (link)). During treatment of borreliosis, doxycycline is detectable in cerebrospinal fluid, both 4 h after ingestion on treatment day 13 (200 mg, orally every 24 h; Karlsson et al., 1996 (link)) and 2–3 h after the last administration on treatment days 5–8 (100 or 200 mg, orally twice a day; Dotevall and Hagberg, 1989 (link)). For consistency with previous studies (Bach et al., 2018b (link), 2019 (link)), we scheduled fear memory acquisition ∼3.5 h after drug ingestion.
According to the manufacturer’s information, the drug’s half-life is ∼16 h. Hence, the drug was cleared >99.9% before the recall session 7 d after ingestion. The drug was manufactured, blinded, and randomized separately for males and females, by a GMP-licensed pharmacy (Kantonsapotheke Zurich). Mannitol was used as placebo. Randomization was broken after the last participant completed the study, data were checked for consistency, and the study analysis plan was preregistered on OSF.

If infected and eligible (above the age of 8, not pregnant, not breast feeding and not having severe illness), participants were invited for treatment through a community-based approach. They were first educated on the duration, the need to adhere to treatment, eat before treatment to avoid side effect, timing of treatment, a place to gather for treatment, reporting side effects and obtaining consent. The infected individuals were grouped by proximity to a CDD who offered them light meal before they swallowed doxycycline 100mg tablet or capsule (Vibramycin, Pfizer in the 1st round; generic doxycycline in 2nd round) every day under the watch of the CDD (directly observed therapy (DOT) strategy) for 35 days. Treatments were monitored for completion and side effects—diarrhoea, nausea, vomiting, headache, itches, skin eruption or others (detailing nature, severity, and frequency) daily by CDDs. This was done through questionnaire or beneficiary complaint. Treatments were noted in treatment register and side effects were noted by ticking or shading the corresponding option (s) in treatment register (See S2 Table).