In a review of the interactions between monogenean parasites and their fish hosts, Buchmann and Lindenstrøm (2002) concluded that "immune evasion mechanisms are probably a main factor in host specificity." Rosengard et al. (2002) noted that the smallpox inhibitor of complement enzymes (SPICE) is nearly 100-fold more potent than the vaccinia homolog in inactivating human C3b and sixfold more potent at inactivating C4b, providing evidence for how variola proteins are particularly adept at overcoming human immunity relative to vaccinia.