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Background Intradermal (ID) rabies vaccination for pre-exposure prophylaxis (PrEP) has become increasingly popular; however, there is limited evidence about the effectiveness of different ID PrEP schedules in travellers aged > 50 years or their response to ID boosters. This study aimed to compare across different ID vaccine schedules and age groups the proportion of travellers who were seropositive after (i) primary course of ID PrEP and (ii) a booster. Methods Travellers who received ID PrEP at a travel medicine clinic in South Australia from 2000 to 2016 were included. Three schedules were examined: 1IDx3 (1 × 0.1 ml on days 0, 7, 21–28), 2IDx2 (2 × 0.1 ml on days 0, 7) and 4IDx1 (4x0.1 ml on day 0). The 4IDx1 is a non-standard schedule that has been previously explored in research settings, but not endorsed by WHO for PrEP. Antibody titres of ≥0.5 IU/ml were considered seropositive. The proportion seropositive after a primary course or post-booster was estimated for each schedule and age category. Predictors of seronegative status after a primary course were examined using multivariable logistic regression models. Results Overall, 835 travellers (median age 37.5 years; 37.1% > 50 years) were included in the analyses of seropositivity after a primary course. Another group of 771 travellers (median age 45.9 years; 43.5% > 50 years) was included in the analyses of seropositivity post-booster. The proportion seropositive after primary course was 92.5% (95%CI: 90.5–94.1%) and highest with the 1IDx3 schedule (93.4%; 95%CI: 91.4–95.0%). After adjusting for age and timing of the serology, the odds of seronegative status were four times higher (OR 4.17; 95%CI: 1.43–12.18) with the 4IDx1 schedule compared to 1IDx3. Overall, 98.7% (95%CI: 97.6–99.3%) were seropositive post-booster. Of 46 travellers who received a booster ≥3 years after PrEP, all were seropositive post-booster. Conclusions In older travellers, the 1IDx3 schedule was the most effective, and a high proportion were seropositive post-booster even many years after a primary course.

When used as pre-travel malaria chemoprophylaxis to enable a 'drug-free holiday', the 3-day atovaquone/proguanil schedule (250mg/100mg, 4 tablets/day for 3 consecutive days) had a high compliance rate of 97.7%, and was well tolerated and accepted by travellers.

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