Malaria despite Doxycycline Prophylaxis: A Case Series and Scoping Review

Travellers to regions with high malaria risk are recommended to take chemoprophylaxis. Although not licensed for malaria chemoprophylaxis in Germany, doxycycline is frequently used, mainly because of its good tolerability and low cost.

We report three cases of patients who developed Plasmodium falciparum (P. falciparum) malaria despite chemoprophylaxis with doxycycline and reported high, though incomplete, adherence. These breakthrough infections after only minor deviations from the recommended prophylaxis prompted a scoping review reported according to PRISMA-ScR in PubMed on the efficacy of doxycycline for chemoprophylaxis of falciparum malaria.

In a search up to June 2026, 13 heterogeneous studies published between 1993 and 2023 were identified. Among these are 2 randomised controlled trials, 2 case-control studies, 5 case reports, and 4 cohort studies comprising a total of at least 2,080 participants. Doxycycline showed a good prophylactic efficacy overall; however, breakthrough infections were repeatedly reported. Even minimal deviations from prophylaxis prescriptions were associated with an increased risk for malaria; risk increased further with declining adherence. Premature stopping of prophylaxis with doxycycline after leaving the endemic area also posed a risk for malaria. Studies have not yet shown clear evidence for clinically relevant doxycycline resistance. Despite the investigation of candidate genes, there are currently no validated markers for resistance in P. falciparum.

Even single missed doses or premature cessation may be associated with a significantly increased risk of failure of doxycycline chemoprophylaxis. Travellers should be explicitly counselled on the importance of consistent chemoprophylaxis and motivated to maintain high adherence.