Probably "while", to emphasize that the holiday (US "vacation") lasted for a while. We could also use "when". With a verb of state, the word "as" would tend to imply a causal relationship, i.e., being on holiday caused Tom to come down with the flu. If we used an inceptive verb with a more perfective aspect, for example "Tom came down with the flu as we began our holiday", that would work quite well with "as" (meaning at the time), or we could use "when". "While" would not work well for such a verb / aspect.