﻿YELLOW 
  FEVER 
  — 
  SAWYER 
  587 
  

  

  yellow 
  fever 
  virus 
  adapted 
  to 
  mice 
  and 
  human 
  immune 
  serum. 
  The 
  

   original 
  method 
  could 
  be 
  used 
  only 
  on 
  a 
  small 
  scale 
  on 
  account 
  of 
  

   the 
  difficulties 
  of 
  obtaining 
  enough 
  of 
  the 
  immune 
  serum. 
  Through 
  

   years 
  of 
  patient 
  research 
  the 
  virulent 
  Asibi 
  strain 
  was 
  so 
  modified 
  

   through 
  tissue 
  culture 
  by 
  Lloyd, 
  Theiler, 
  and 
  Eicci 
  (1936) 
  and 
  Theiler 
  

   and 
  Smith 
  (1937) 
  that 
  its 
  lowered 
  virulence 
  made 
  possible 
  its 
  use 
  

   without 
  serum. 
  At 
  the 
  same 
  time, 
  the 
  use 
  of 
  chick 
  embryo 
  tissues 
  in 
  

   place 
  of 
  the 
  brains 
  of 
  living 
  mice 
  in 
  producing 
  the 
  vaccine 
  reduced 
  the 
  

   risk 
  of 
  the 
  introduction 
  of 
  unknown 
  pathogenic 
  viruses, 
  thus 
  increas- 
  

   ing 
  the 
  element 
  of 
  safety. 
  After 
  the 
  experience 
  of 
  Findlay 
  and 
  Mac- 
  

   Callum 
  (1937) 
  and 
  Soper 
  and 
  Smith 
  (1938a) 
  with 
  delayed 
  infections 
  

   characterized 
  by 
  jaundice 
  after 
  yellow 
  fever 
  vaccination 
  with 
  tissue 
  

   culture 
  material, 
  used 
  in 
  the 
  latter 
  case 
  along 
  with 
  hyperimmune 
  

   serum, 
  the 
  possibility 
  of 
  the 
  introduction 
  of 
  an 
  unknown 
  virus 
  into 
  the 
  

   vaccine 
  from 
  the 
  blood 
  of 
  apparently 
  healthy 
  human 
  donors 
  became 
  a 
  

   matter 
  of 
  concern. 
  As 
  a 
  result, 
  human 
  serum 
  used 
  in 
  the 
  tissue 
  cul- 
  

   tures 
  is 
  now 
  being 
  inactivated 
  with 
  heat. 
  2 
  Any 
  reports 
  of 
  jaundice 
  

   or 
  other 
  symptoms 
  following 
  vaccination 
  are 
  being 
  carefully 
  investi- 
  

   gated. 
  One 
  such 
  report 
  in 
  1939 
  is 
  still 
  under 
  study 
  in 
  Brazil 
  to 
  find 
  

   out 
  its 
  possible 
  relationship 
  to 
  the 
  vaccine. 
  With 
  the 
  present 
  pre- 
  

   cautions 
  the 
  tissue 
  culture 
  vaccine 
  17D 
  would 
  seem 
  to 
  have 
  as 
  high 
  a 
  

   degree 
  of 
  safety 
  for 
  the 
  vaccinated 
  person 
  as 
  could 
  be 
  expected 
  of 
  a 
  

   biological 
  product 
  containing 
  a 
  living 
  virus. 
  That 
  the 
  infection 
  is 
  

   not 
  likely 
  to 
  be 
  spread 
  from 
  vaccinated 
  persons 
  to 
  others 
  through 
  the 
  

   medium 
  of 
  mosquitoes 
  and 
  finally 
  to 
  revert 
  to 
  a 
  more 
  virulent 
  form 
  

   has 
  been 
  shown 
  by 
  the 
  studies 
  of 
  Roubaud 
  and 
  his 
  associates 
  (1937) 
  

   and 
  Whitman 
  (1939). 
  

  

  As 
  to 
  the 
  effectiveness 
  of 
  the 
  vaccine 
  made 
  from 
  strain 
  17D, 
  there 
  

   has 
  been 
  much 
  recent 
  evidence. 
  Reports 
  by 
  Smith, 
  Penna, 
  and 
  

   Paoliello 
  (1938) 
  and 
  by 
  Soper 
  and 
  Smith 
  (1938b) 
  showed 
  a 
  high 
  

   percentage 
  of 
  immunes 
  among 
  vaccinated 
  persons 
  whose 
  blood 
  was 
  

   afterward 
  tested 
  by 
  the 
  mouse-protection 
  test. 
  At 
  the 
  end 
  of 
  1938 
  

   and 
  early 
  in 
  1939, 
  however, 
  the 
  results 
  with 
  certain 
  lots 
  of 
  vaccine 
  

   were 
  not 
  so 
  happy, 
  as 
  reported 
  by 
  Soper, 
  Smith, 
  and 
  Penna 
  (1940). 
  

   While 
  90 
  percent 
  of 
  persons 
  tested 
  after 
  vaccination 
  earlier 
  in 
  1938 
  

   had 
  developed 
  protective 
  antibodies 
  in 
  their 
  blood, 
  and 
  field 
  experience 
  

   in 
  the 
  presence 
  of 
  epidemics 
  had 
  suggested 
  that 
  vaccinated 
  groups 
  

   were 
  protected 
  against 
  natural 
  infection 
  as 
  early 
  as 
  1 
  week 
  after 
  

   the 
  inoculation, 
  a 
  considerable 
  number 
  of 
  persons 
  vaccinated 
  at 
  the 
  

   time 
  mentioned 
  and 
  later 
  exposed 
  to 
  an 
  anticipated 
  epidemic 
  developed 
  

   yellow 
  fever. 
  Among 
  136,000 
  persons 
  vaccinated 
  with 
  15 
  different 
  

   lots 
  of 
  vaccine, 
  there 
  were 
  56 
  cases 
  and 
  14 
  deaths 
  from 
  7 
  days 
  to 
  14 
  

  

  7 
  Subsequent 
  to 
  the 
  presentation 
  of 
  this 
  paper 
  there 
  has 
  been 
  further 
  observation 
  of 
  

   jaundice 
  after 
  vaccination 
  against 
  yellow 
  fever, 
  and 
  methods 
  have 
  been 
  perfected 
  and 
  

   adopted 
  for 
  completely 
  omitting 
  normal 
  human 
  serum 
  in 
  manufacture. 
  

  

  