American foulbrood (AFB), caused by the spore-forming bacterium Paenibacillus
larvae, is the most destructive bacterial brood disease of Apis mellifera. Control
is challenging because endospores persist for decades and antibiotic use is
restricted by regulations, resistance, and residue concerns. Bacteriophages
have re-emerged as a species-specific, residue-free strategy for AFB prevention
and treatment. A PRISMA-guided systematic review was conducted searching
PubMed, Embase, and Web of Science using the terms (bacteriophage OR
phage) AND (honeybee OR Apis mellifera). A total of 90 records were retrieved;
after deduplication (19 removed), 71 titles and abstracts were screened. Eleven
full texts were assessed for eligibility. Nine studies met inclusion criteria: three in
adult bees or colonies, four in larvae, and two in vitro. Across studies, 27 P. larvae
phages were characterized in vitro, 18 tested in larval assays, and nine evaluated
at the hive level, mainly via oral delivery. In a controlled hive trial, a three-phage
cocktail provided complete protection from natural AFB (100% protected vs. 80%
infection in controls; p < 0.05) and enabled full recovery within 2 weeks, performing
comparably to or better than prophylactic antibiotics. Larval studies generally
showed significantly improved survival with prophylactic or therapeutic dosing,
though efficacy varied by phage. A biodistribution study found limited indirect
larval exposure after adult feeding (~32 PFU/larva at 24 h), indicating hive-mediated
inactivation as a key translational barrier. One phage bound both vegetative
cells and spores while retaining ~93% in-vitro infectivity. Overall, phage cocktails
show strong proof-of-concept, with formulation, delivery, and rational cocktail
design as key translational priorities.