Towards_II a_AT1 sane_JJ and_CC rational_JJ approach_NN1 to_II management_NN1 of_IO Influenza_NP1 H1N1_FO 2009_MC Introduction_NN1 On_II April_NPM1 9_MC ,_, 2009_MC it_PPH1 became_VVD apparent_JJ to_II public_JJ health_NN1 officials_NN2 in_II Mexico_NP1 City_NN1 that_CST an_AT1 outbreak_NN1 of_IO influenza_NN1 was_VBDZ in_II progress_NN1 late_RR in_II the_AT influenza_NN1 season_NNT1 ._. 
On_II April_NPM1 17_MC ,_, two_MC cases_NN2 in_II children_NN2 were_VBDR also_RR reported_VVN in_II California_NP1 near_II the_AT Mexican_JJ border_NN1 ._. 
Virus_NN1 samples_NN2 were_VBDR obtained_VVN and_CC the_AT virus_NN1 determined_VVN to_TO be_VBI a_AT1 novel_JJ strain_NN1 of_IO influenza_NN1 A_ZZ1 of_IO the_AT H1N1_FO serotype_NN1 ._. 
Preliminary_JJ tests_NN2 conducted_VVN by_II the_AT Centers_NN2 for_IF Disease_NN1 Control_NN1 and_CC Prevention_NN1 (_( CDC_NP1 )_) indicated_VVD that_CST the_AT virus_NN1 was_VBDZ a_AT1 novel_JJ reassortant_NN1 ,_, containing_VVG genetic_JJ elements_NN2 of_IO influenza_NN1 viruses_NN2 found_VVN in_II swine_NN ,_, birds_NN2 and_CC human_JJ beings_NN2 ._. 
Influenza_NN1 virus_NN1 ,_, an_AT1 enveloped_JJ virus_NN1 of_IO the_AT Orthomyxoviridae_NP1 family_NN1 ,_, has_VHZ a_AT1 unique_JJ capacity_NN1 for_IF genetic_JJ variation_NN1 that_CST is_VBZ based_VVN in_II two_MC molecular_JJ features_NN2 of_IO the_AT virus_NN1 family_NN1 ._. 
First_MD of_IO all_DB ,_, the_AT surface_NN1 proteins_NN2 of_IO the_AT virus_NN1 are_VBR highly_RR variable_JJ ,_, able_JK to_TO mutate_VVI up_RG21 to_RG22 50%_NNU of_IO their_APPGE amino_NN1 acid_NN1 sequence_NN1 and_CC still_RR perform_VV0 their_APPGE functions_NN2 in_II infection_NN1 ._. 
Secondly_RR ,_, the_AT viral_JJ genome_NN1 is_VBZ segmented_VVN ,_, with_IW eight_MC RNA_NN1 segments_VVZ that_CST are_VBR genetically_RR independent_JJ of_IO one_PPX121 another_PPX122 ._. 
In_II a_AT1 mixed_JJ infection_NN1 of_IO different_JJ influenza_NN1 genotypes_NN2 ,_, these_DD2 segments_NN2 can_VM almost_RR randomly_RR reassort_VVI resulting_VVG in_II hybrid_JJ genotypes_NN2 with_IW some_DD segments_NN2 derived_VVN from_II one_MC1 virus_NN1 strain_NN1 ,_, while_CS the_AT other_JJ segments_NN2 are_VBR derived_VVN from_II a_AT1 second_MD strain_NN1 ._. 
Less_DAR than_CSN one_MC1 month_NNT1 later_RRR ,_, hundreds_NNO2 of_IO probable_JJ cases_NN2 of_IO infection_NN1 by_II this_DD1 novel_JJ virus_NN1 ,_, designated_VVD Influenza_NP1 H1N12009_FO ,_, had_VHD been_VBN identified_VVN ,_, with_IW 26_MC deaths_NN2 ,_, centered_VVD about_II the_AT area_NN1 of_IO Mexico_NP1 City_NN1 ._. 
An_AT1 additional_JJ several_DA2 hundred_NNO probable_JJ cases_NN2 had_VHD been_VBN identified_VVN in_II the_AT United_NP1 States_NP1 ,_, most_RRT associated_VVN with_IW recent_JJ travel_NN1 to_II Mexico_NP1 ,_, and_CC concentrated_VVN in_II California_NP1 ,_, Texas_NP1 and_CC New_NP1 York_NP1 ._. 
Sporadic_JJ cases_NN2 ,_, also_RR associated_VVN with_IW travel_NN1 to_II Mexico_NP1 in_II large_JJ part_NN1 ,_, were_VBDR found_VVN in_II several_DA2 European_JJ countries_NN2 as_RR21 well_RR22 ._. 
The_AT World_NN1 Health_NN1 Organization_NN1 (_( WHO_NP1 )_) began_VVD to_TO declare_VVI ever_RR higher_JJR stages_NN2 on_II its_APPGE "_" pandemic_JJ "_" scale_NN1 ,_, designating_VVG the_AT novel_JJ Influenza_NP1 H1N1_FO 2009_MC a_AT1 potential_JJ threat_NN1 to_II world-_JJ wide_JJ health_NN1 ._. 
Press_VV0 coverage_NN1 and_CC involvement_NN1 of_IO public_JJ officials_NN2 in_II the_AT response_NN1 to_II the_AT novel_JJ virus_NN1 has_VHZ reached_VVN epic_JJ proportions_NN2 ._. 
This_DD1 commentary_NN1 is_VBZ intended_VVN to_TO review_VVI and_CC analyze_VVI the_AT salient_JJ facts_NN2 of_IO the_AT outbreak_NN1 and_CC the_AT molecular_JJ sequence_NN1 of_IO the_AT principal_JJ external_JJ antigens_NN2 of_IO Influenza_NP1 H1N12009_FO ._. 
The_AT discussion_NN1 will_VM focus_VVI on_II the_AT implications_NN2 of_IO this_DD1 analysis_NN1 for_IF the_AT continued_JJ course_NN1 of_IO the_AT outbreak_NN1 and_CC the_AT medical_JJ response_NN1 ._. 
Discussion_NN1 Tenor_NN1 of_IO the_AT Response_NN1 to_II Influenza_NP1 H1N1_FO 2009Actions_FO concerning_II Flu_NN1 H1N1_FO 2009_MC need_VV0 to_TO be_VBI based_VVN on_II fact_NN1 and_CC science_NN1 ,_, following_VVG recommendations_NN2 of_IO public_JJ health_NN1 officials_NN2 ,_, and_CC not_XX fueled_VVN by_II political_JJ ,_, legal_JJ or_CC media_NN interests_NN2 and_CC hysteria_NN1 ._. 
This_DD1 is_VBZ time_NNT1 for_IF calm_NN1 ,_, thoughtful_JJ action_NN1 ,_, and_CC not_XX the_AT panic_NN1 we_PPIS2 have_VH0 seen_VVN spread_NN1 around_II the_AT globe_NN1 inspired_VVN by_II media_NN reports_NN2 ._. 
When_CS 10_MC schools_NN2 or_CC an_AT1 entire_JJ school_NN1 district_NN1 are_VBR closed_VVN due_II21 to_II22 one_MC1 suspected_JJ case_NN1 of_IO influenza_NN1 ,_, we_PPIS2 might_VM well_RR ask_VVI if_CSW our_APPGE response_NN1 has_VHZ been_VBN measured_VVN and_CC appropriate_JJ ._. 
The_AT good_JJ faith_NN1 of_IO the_AT public_NN1 is_VBZ a_AT1 precious_JJ commodity_NN1 ._. 
When_CS one_MC1 day_NNT1 a_AT1 pandemic_JJ is_VBZ trumpeted_VVN ,_, and_CC the_AT next_MD day_NNT1 the_AT outbreak_NN1 is_VBZ called_VVN no_AT more_DAR than_CSN normal_JJ flu_NN1 and_CC under_II control_NN1 ,_, and_CC then_RT a_AT1 call_NN1 goes_VVZ out_RP for_IF a_AT1 multibillion_NN1 dollar_NNU1 vaccine_NN1 program_NN1 to_TO defend_VVI against_II a_AT1 major_JJ pandemic_JJ ,_, one_PN1 risks_VVZ the_AT public_JJ feeling_NN1 whiplash_NN1 and_CC the_AT credibility_NN1 of_IO public_JJ officials_NN2 being_VBG damaged_VVN ._. 
Further_RRR ,_, every_AT1 measure_NN1 of_IO response_NN1 has_VHZ a_AT1 cost-benefit_JJ ratio_NN1 that_CST needs_VVZ to_TO be_VBI carefully_RR considered_VVN ,_, which_DDQ is_VBZ best_RRT done_VDN in_II collaboration_NN1 with_IW public_JJ health_NN1 professionals_NN2 ._. 
We_PPIS2 have_VH0 seen_VVN unnecessary_JJ and_CC useless_JJ quarantines_NN2 ,_, interdictions_NN2 of_IO trade_NN1 and_CC excessive_JJ closures_NN2 which_DDQ can_VM not_XX be_VBI sustained_VVN and_CC have_VH0 little_RR if_CS any_DD benefit_NN1 ._. 
Travel_VV0 in_RP and_CC out_II21 of_II22 Mexico_NP1 has_VHZ been_VBN severely_RR disrupted_VVN ,_, but_CCB not_XX to_II New_NP1 York_NP1 City_NN1 which_DDQ also_RR has_VHZ many_DA2 confirmed_VVN cases_NN2 ._. 
A_AT1 cruise_NN1 ship_NN1 plies_VVZ the_AT Pacific_NP1 ,_, avoiding_VVG Mexican_JJ ports_NN2 with_IW little_JJ or_CC no_AT influenza_NN1 activity_NN1 ,_, but_CCB plans_VVZ to_TO host_VVI its_APPGE passengers_NN2 an_AT1 extra_JJ night_NNT1 in_II San_NP1 Diego_NP1 ,_, with_IW a_AT1 higher_JJR number_NN1 of_IO H1N1_FO cases_NN2 in_II the_AT area_NN1 than_CSN most_DAT areas_NN2 of_IO Mexico_NP1 ._. 
At_II some_DD point_NN1 in_II what_DDQ will_VM probably_RR be_VBI a_AT1 long_JJ engagement_NN1 with_IW this_DD1 new_JJ influenza_NN1 strain_NN1 ,_, a_AT1 more_RGR precisely_RR targeted_VVN and_CC rational_JJ response_NN1 will_VM be_VBI needed_VVN ._. 
Changes_NN2 in_II the_AT Neuraminidase_NN1 The_AT second_MD external_JJ protein_NN1 of_IO influenza_NN1 virus_NN1 ,_, constituting_VVG 20-25%_FO of_IO the_AT surface_NN1 proteins_NN2 ,_, is_VBZ the_AT N_ND1 antigen_NN1 ._. 
This_DD1 protein_NN1 is_VBZ an_AT1 enzyme_NN1 named_VVN neuraminidase_NN1 for_IF its_APPGE ability_NN1 to_TO cleave_VVI neuraminic_JJ or_CC sialic_JJ acid_NN1 from_II complex_JJ carbohydrates_NN2 such_II21 as_II22 mucins_NN2 ._. 
In_II infection_NN1 it_PPH1 serves_VVZ to_TO allow_VVI release_NN1 of_IO newly_RR produced_VVN virus_NN1 from_II surface_NN1 receptors_NN2 and_CC to_TO digest_VVI mucous_NN1 secretions_NN2 ,_, allowing_VVG the_AT virus_NN1 better_JJR access_NN1 to_II the_AT surface_NN1 of_IO susceptible_JJ cells_NN2 and_CC spread_VVN through_II the_AT respiratory_JJ tract_NN1 ._. 
Its_APPGE value_NN1 as_II a_AT1 spreading_JJ factor_NN1 is_VBZ underscored_VVN by_II the_AT fact_NN1 that_CST the_AT currently_RR licensed_JJ anti-_JJ viral_JJ drugs_NN2 oseltamivir_NN1 (_( Tamiflu_NP1 )_) and_CC zanamivir_NN1 (_( Relenza_NP1 )_) function_NN1 as_CSA neuraminidase_NN1 inhibitors_NN2 ._. 
In_II the_AT absence_NN1 of_IO herd_NN1 immunity_NN1 to_II the_AT H_NP1 antigen_NN1 ,_, partial_JJ protection_NN1 can_VM be_VBI provided_VVN if_CS the_AT same_DA or_CC similar_JJ N_ZZ1 antigen_NN1 is_VBZ retained_VVN ._. 
Eickhoff_VV0 and_CC Meiklejohn_NP1 showed_VVD that_CST the_AT infection_NN1 rate_NN1 with_IW the_AT H3N2_FO virus_NN1 was_VBDZ reduced_VVN up_RG21 to_RG22 50%_NNU in_II Air_NN1 Force_NN1 cadets_NN2 who_PNQS had_VHD received_VVN the_AT H2N2_FO vaccine_NN1 ,_, due_II21 to_II22 the_AT shared_JJ N2_FO antigen_NN1 remaining_VVG identical_JJ ._. 
If_CS the_AT N1_FO antigen_NN1 of_IO the2009_FO virus_NN1 proved_VVD to_TO be_VBI similar_JJ to_II that_DD1 of_IO 2008_MC ,_, even_RR with_IW an_AT1 antigenic_JJ shift_NN1 in_II H_ZZ1 ,_, then_RT some_DD cross_NN1 protection_NN1 from_II prior_JJ H1N1_FO infection_NN1 or_CC the_AT 2008_MC vaccine_NN1 might_VM be_VBI expected_VVN ._. 
Unfortunately_RR ,_, in_II the_AT case_NN1 of_IO influenza_NN1 H1N12009_FO ,_, the_AT N1_FO antigen_NN1 also_RR is_VBZ significantly_RR novel_JJ ,_, differing_VVG by_II 18.2%_FO from_II the_AT 2008_MC H1N1_FO virus_NN1 ._. 
While_CS the_AT antigenic_JJ sites_NN2 within_II the_AT N_ND1 antigen_NN1 are_VBR less_RGR well_RR defined_VVN ,_, the_AT pattern_NN1 of_IO changes_NN2 in_II the_AT N_ND1 antigen_NN1 of_IO the_AT 2009_MC virus_NN1 (_( not_XX shown_VVN )_) are_VBR not_XX encouraging_JJ ._. 
No_AT cross_NN1 protection_NN1 is_VBZ likely_JJ ._. 
Implications_NN2 from_II Sequence_NN1 Changes_NN2 in_II H1N1_FO 2009_MC Overall_JJ ,_, it_PPH1 is_VBZ clear_JJ from_II the_AT sequence_NN1 alignments_NN2 of_IO the_AT Influenza_NP1 H1N1_FO 2009_MC virus_NN1 that_CST ,_, even_CS21 though_CS22 this_DD1 virus_NN1 is_VBZ still_RR basically_RR in_II the_AT family_NN1 of_IO H1N1_FO viruses_NN2 ,_, the_AT sequence_NN1 changes_NN2 indicate_VV0 a_AT1 significant_JJ antigenic_JJ shift_NN1 in_II both_DB2 surface_NN1 antigens_NN2 ._. 
The_AT last_MD time_NNT1 such_DA an_AT1 antigenic_JJ shift_NN1 occurred_VVD in_RP both_RR H_ZZ1 and_CC N_ZZ1 antigens_NN2 was_VBDZ the_AT 1957_MC Asian_JJ H2N2_FO pandemic_JJ ._. 
A_AT1 factor_NN1 present_NN1 in_II 1957_MC was_VBDZ that_CST there_EX was_VBDZ serological_JJ evidence_NN1 that_CST those_DD2 over_RG 60_MC years_NNT2 of_IO age_NN1 retained_VVD an_AT1 anti-_NN1 H2N2_FO antibody_NN1 response_NN1 from_II prior_JJ exposure_NN1 to_II the_AT virus_NN1 before_II 1900_MC ._. 
This_DD1 blunted_JJ the_AT effect_NN1 of_IO the_AT 1957_MC pandemic_JJ in_II the_AT elderly_JJ ._. 
This_DD1 factor_NN1 is_VBZ not_XX expected_VVN in_II the_AT case_NN1 of_IO H1N1_FO 2009_MC ,_, since_CS there_EX is_VBZ no_AT evidence_NN1 that_CST a_AT1 virus_NN1 with_IW a_AT1 similar_JJ antigenic_JJ profile_NN1 has_VHZ circulated_VVN in_II the_AT human_JJ population_NN1 in_RP over_RG 100_MC years_NNT2 ._. 
Neither_RR Swine_NN Nor_CC Mexico_NP1 Are_VBR to_TO Blame_VV0 The_AT outbreak_NN1 is_VBZ due_II21 to_II22 a_AT1 rare_JJ recombination_NN1 of_IO influenza_NN1 gene_NN1 segments_NN2 from_II swine_NN with_IW avian_JJ and_CC human_JJ influenza_NN1 ._. 
Once_RR this_DD1 one_PN1 time_VV0 event_NN1 occurred_VVD ,_, swine_NN are_VBR not_XX a_AT1 significant_JJ immediate_JJ source_NN1 of_IO the_AT human_JJ version_NN1 of_IO influenza_NN1 H1N1_FO 2009_MC ,_, and_CC the_AT virus_NN1 can_VM not_XX be_VBI acquired_VVN from_II handling_VVG or_CC eating_VVG pork_NN1 ._. 
The_AT consensus_NN1 among_II virologists_NN2 is_VBZ that_CST the_AT actual_JJ natural_JJ host_NN1 and_CC ultimate_JJ source_NN1 of_IO influenza_NN1 variants_NN2 is_VBZ migratory_JJ waterfowl_NN1 ._. 
The_AT prospective_JJ slaughter_NN1 of_IO pigs_NN2 in_II Egypt_NP1 ,_, and_CC the_AT international_JJ interdiction_NN1 of_IO imported_JJ pork_NN1 ,_, have_VH0 no_AT rational_JJ basis_NN1 in_II science_NN1 or_CC public_JJ health_NN1 ._. 
Factors_NN2 Predisposing_VVG to_II Control_NN1 of_IO Influenza_NP1 H1N1_FO 2009_MC Two_MC additional_JJ facts_NN2 concerning_II the_AT virus_NN1 are_VBR positive_JJ ._. 
First_MD ,_, while_CS the_AT most_RGT successful_JJ pandemic_JJ influenza_NN1 viruses_NN2 have_VH0 changed_VVN only_RR the_AT H_ZZ1 and_CC N_ZZ1 antigens_NN2 and_CC retained_VVD the_AT same_DA human_JJ core_NN1 proteins_NN2 of_IO the_AT virus_NN1 ,_, influenza_NN1 H1N1_FO 2009_MC has_VHZ several_DA2 more_DAR components_NN2 from_II ani-_JJ mal_JJ flu_NN1 strains_NN2 than_CSN the_AT H2N2_FO and_CC H3N2_FO viruses_NN2 of_IO 1957_MC and_CC 1968_MC ,_, respectively_RR ._. 
This_DD1 may_VM make_VVI the_AT 2009_MC virus_NN1 less_RGR compatible_JJ with_IW effective_JJ replication_NN1 in_II humans_NN2 ,_, which_DDQ may_VM in_II turn_VVI be_VBI holding_VVG it_PPH1 back_RP in_II its_APPGE penetrance_NN1 of_IO the_AT human_JJ population_NN1 ._. 
Second_MD ,_, the_AT 2009_MC virus_NN1 is_VBZ sensitive_JJ to_II the_AT two_MC neuraminidase_NN1 inhibitors_NN2 licensed_VVN as_CSA antiviral_JJ drugs_NN2 ._. 
A_AT1 reasonable_JJ conclusion_NN1 from_II these_DD2 last_MD two_MC facts_NN2 is_VBZ that_CST there_EX is_VBZ no_AT evidence_NN1 at_II all_DB that_CST this_DD1 is_VBZ a_AT1 bioterror_NN1 event_NN1 ,_, but_CCB rather_RG a_AT1 novel_JJ virus_NN1 perpetrated_VVD by_II nature_NN1 alone_RR ._. 
Future_JJ Strategies_NN2 There_EX is_VBZ also_RR need_VV0 for_IF enhanced_JJ influenza_NN1 research_NN1 and_CC development_NN1 ._. 
The_AT priority_NN1 of_IO influenza_NN1 waned_VVD in_II the_AT absence_NN1 of_IO a_AT1 pandemic_JJ ,_, coupled_VVN with_IW the_AT availability_NN1 of_IO drugs_NN2 and_CC what_DDQ seemed_VVD to_TO be_VBI adequate_JJ vaccine_NN1 technology_NN1 ._. 
However_RR ,_, the_AT antivirals_NN2 will_VM never_RR have_VHI been_VBN used_JJ to_II the_AT extent_NN1 that_CST is_VBZ likely_JJ should_VM this_DD1 H1N1_FO 2009_MC outbreak_NN1 continue_VV0 ._. 
If_CS resistance_NN1 to_II these_DD2 antivirals_NN2 were_VBDR to_TO develop_VVI due_II21 to_II22 their_APPGE overuse_NN1 and_CC misuse_NN1 ,_, much_DA1 as_CSA in_II the_AT case_NN1 of_IO antibiotics_NN2 for_IF bacteria_NN2 ,_, then_RT there_EX is_VBZ currently_RR no_AT backup_NN1 drug_NN1 to_TO combat_VVI the_AT virus_NN1 ._. 
Antivirals_NN2 that_CST inhibit_VV0 infection_NN1 and_CC fusion_NN1 have_VH0 been_VBN developed_VVN for_IF viruses_NN2 such_II21 as_II22 human_JJ immunodeficiency_NN1 virus_NN1 (_( HIV_NP1 )_) that_CST have_VH0 very_RG similar_JJ entry_NN1 mechanisms_NN2 ,_, and_CC should_VM be_VBI developed_VVN for_IF influenza_NN1 as_RR21 well_RR22 ._. 
As_II21 for_II22 the_AT influenza_NN1 vaccine_NN1 ,_, it_PPH1 is_VBZ still_RR produced_VVN by_II relatively_RR archaic_JJ methods_NN2 developed_VVN in_II the_AT 1930s_MC2 to_II 1950s_MC2 using_VVG mass_JJ quantities_NN2 of_IO embryonated_JJ chicken_NN1 eggs_NN2 ._. 
We_PPIS2 are_VBR not_XX far_RR beyond_II the_AT pioneering_JJ days_NNT2 of_IO Goodpasture_NP1 ,_, Woodruff_NP1 ,_, Buddingh_NP1 and_CC Francis_NP1 in_II this_DD1 regard_NN1 ._. 
Each_DD1 dose_NN1 of_IO flu_NN1 vaccine_NN1 requires_VVZ the_AT use_NN1 of_IO 1.2_MC live_JJ eggs_NN2 ,_, or_CC about_RG 600_MC million_NNO embryonated_JJ eggs_NN2 to_TO produce_VVI 500_MC mil-_JJ lion_NN1 does_VDZ of_IO virus_NN1 for_IF 6.77_MC billion_NNO people_NN ._. 
The_AT math_NN1 is_VBZ not_XX encouraging_JJ ._. 
Vaccines_NN2 targeting_VVG viruses_NN2 such_II21 as_II22 measles_NN ,_, mumps_NN2 ,_, rubella_NN1 and_CC hepatitis_NN1 B_ZZ1 employ_VV0 cell_NN1 culture_NN1 or_CC recombinant_JJ technologies_NN2 and_CC have_VH0 superior_JJ safety_NN1 characteristics_NN2 ._. 
Programs_NN2 for_IF greater_JJR efficiency_NN1 in_II producing_VVG effective_JJ and_CC safe_JJ influenza_NN1 vaccines_NN2 have_VH0 been_VBN too_RG long_RR delayed_VVN in_II development_NN1 and_CC need_VV0 to_TO be_VBI implemented_VVN quickly_RR ,_, to_TO assure_VVI that_CST this_DD1 and_CC future_JJ threats_NN2 of_IO pandemic_JJ influenza_NN1 can_VM be_VBI met_VVN ._. 
Over_II the_AT long_JJ run_NN1 ,_, immunization_NN1 provides_VVZ the_AT best_JJT preventive_JJ strategy_NN1 against_II influenza_NN1 virus_NN1 ._. 
Critics_NN2 revel_VV0 in_II citing_VVG the_AT 1976_MC swine_NN flu_NN1 vaccine_NN1 ,_, which_DDQ produced_VVD 25_MC vaccine-associated_JJ deaths_NN2 due_II21 to_II22 Guillain-Barre_NP1 syndrome_NN1 while_CS the_AT virus_NN1 itself_PPX1 only_RR resulted_VVN in_II one_MC1 death_NN1 at_II Ft_NNU ._. 
Dix_MC ,_, New_NP1 Jersey_NP1 ._. 
However_RR ,_, such_DA vaccine-bashing_NN1 ignores_VVZ the_AT fact_NN1 that_CST this_DD1 fatal_JJ complication_NN1 occurred_VVD in_RP only_RR 1_MC1 in_II a_AT1 million_NNO vaccinees_NN2 ,_, and_CC was_VBDZ not_XX seen_VVN either_RR before_CS or_CC since_CS that_DD1 immunization_NN1 campaign_NN1 ._. 
Many_DA2 hundreds_NNO2 of_IO mil-_JJ lions_NN2 of_IO doses_NN2 of_IO trivalent_JJ H1_FO ,_, H3_FO and_CC B_ZZ1 influenza_NN1 vaccine_NN1 have_VH0 been_VBN administered_VVN over_II the_AT intervening_JJ 30_MC years_NNT2 without_IW significant_JJ complications_NN2 ,_, while_CS saving_VVG countless_JJ lives_NN2 ._. 
As_II a_AT1 patient_NN1 with_IW significant_JJ cardiopulmonary_JJ disability_NN1 ,_, I_PPIS1 have_VH0 had_VHN clinical_JJ influenza_NN1 three_MC times_NNT2 in_II my_APPGE life_NN1 ,_, in_II 1948,1965_MC and_CC 1974_MC ,_, and_CC been_VBN hospitalized_VVN twice_RR with_IW secondary_JJ pneumococcal_JJ pneumonia_NN1 ._. 
Since_II 1977_MC I_PPIS1 have_VH0 been_VBN routinely_RR administered_VVN the_AT influenza_NN1 vaccine_NN1 ,_, and_CC not_XX only_RR have_VH0 I_PPIS1 been_VBN free_JJ of_IO influenza_NN1 since_II then_RT ,_, but_CCB have_VH0 twice_RR nursed_VVN a_AT1 spouse_NN1 to_II health_NN1 through_II influenza_NN1 ._. 
To_II those_DD2 critics_NN2 of_IO influenza_NN1 immunization_NN1 I_PPIS1 can_VM only_RR say_VVI that_CST I_PPIS1 am_VBM certain_JJ that_CST I_PPIS1 would_VM choose_VVI immunization_NN1 over_II the_AT disease_NN1 ,_, even_RR at_II the_AT risk_NN1 of_IO complications_NN2 or_CC the_AT rare_JJ possibility_NN1 of_IO a_AT1 vaccine-associated_JJ death_NN1 ._. 
To_TO be_VBI frank_JJ ,_, when_CS I_PPIS1 look_VV0 at_II the_AT changes_NN2 in_II the_AT H1N1_FO 2009_MC hemagglutinin_NN1 from_II the_AT 2008_MC virus_NN1 ,_, I_PPIS1 see_VV0 in_II them_PPHO2 the_AT face_NN1 of_IO my_APPGE possible_JJ executioner_NN1 ._. 
Overall_RR ,_, development_NN1 of_IO antiviral_JJ immunizations_NN2 have_VH0 long_RR been_VBN recognized_VVN as_II the_AT most_RRT cost_VV0 efficient_JJ use_NN1 of_IO pub-_JJ lic_JJ dollars_NNU2 in_II the_AT entire_JJ health_NN1 field_NN1 ,_, both_RR in_II lives_NN2 saved_VVN and_CC economic_JJ impact_NN1 ._. 
ConclusionInfluenza_NN1 H1N1_FO 2009_MC is_VBZ a_AT1 novel_JJ virus_NN1 quite_RG unlike_JJ even_RR the_AT other_JJ H1N1_FO influenza_NN1 viruses_NN2 that_CST have_VH0 preceded_VVN it_PPH1 as_CSA agents_NN2 of_IO human_JJ influenza_NN1 ._. 
The_AT fact_NN1 that_CST its_APPGE hemagglutinin_NN1 is_VBZ 27.2%_FO different_JJ and_CC its_APPGE neuraminidase_NN1 is_VBZ 18.2%_FO different_JJ in_II amino_NN1 acid_NN1 sequence_NN1 from_II the_AT 2008_MC H1N1_FO and_CC vaccine_NN1 virus_NN1 strains_NN2 give_VV0 Influenza_NP1 H1N1_FO 2009_MC significant_JJ pandemic_JJ potential_NN1 ,_, based_VVN on_II historical_JJ pandemics_NN1 of_IO the20th_FO century_NNT1 ._. 
However_RR ,_, it_PPH1 has_VHZ yet_RR to_TO prove_VVI that_DD1 potential_NN1 in_II what_DDQ is_VBZ an_AT1 outbreak_NN1 with_IW low_JJ community_NN1 attack_NN1 rates_NN2 and_CC modest_JJ virulence_NN1 ._. 
Further_JJR evolution_NN1 of_IO the_AT virus_NN1 toward_II a_AT1 more_RGR efficient_JJ agent_NN1 of_IO human_JJ disease_NN1 may_VM yet_RR enable_VVI it_PPH1 to_TO produce_VVI a_AT1 major_JJ pandemic_JJ ._. 
The_AT future_JJ course_NN1 of_IO the_AT out-_JJ break_NN1 can_VM not_XX be_VBI predicted_VVN ,_, but_CCB prudence_NN1 dictates_VVZ that_CST a_AT1 new_JJ influenza_NN1 vaccine_NN1 ,_, targeted_VVN to_II the_AT novel_JJ influenza_NN1 H1N1_FO 2009_MC sequence_NN1 be_VBI quickly_RR developed_VVN and_CC prepared_VVN for_IF worldwide_JJ administration_NN1 ._. 
In_II the_AT absence_NN1 of_IO existing_JJ human_JJ "_" herd_NN1 "_" immunity_NN1 to_II this_DD1 virus_NN1 ,_, only_JJ immunization_NN1 provides_VVZ a_AT1 significant_JJ hope_NN1 of_IO suppressing_VVG the_AT long-term_JJ impact_NN1 of_IO this_DD1 newly_RR emergent_JJ virus_NN1 ._. 
