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Date: Mon, 6 Jan 1992 14:22:19 -0500 (EST)
From: SEOVE@MARS.LERC.NASA.gov (ERIC OVERTON)
Message-Id: <920106142219.20401eb3@MARS.LERC.NASA.GOV>
Subject: HIV infected infants
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                                   Articles
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       IgA Antibody Test Reveals HIV Status of Infants 3-6 Months of Age
 
             National Institute of Allergy and Infectious Diseases
                                  U P D A T E
 
      Tuesday, December 24, 1991                            Greg Folkers
                                                            (301) 496-5717
 
                       
      A rapid,  simple,  and inexpensive blood test can reliably identify  HIV 
infection in babies as young as 3 to 6 months of age,  according to a study of 
320 infants in Baltimore, Maryland,  and Port au Prince,  Haiti.  The research 
report  appears  in the December 25 edition of Journal of the American Medical 
Association.  
      The study, supported by the National Institute of Allergy and Infectious 
Diseases, confirms previous research that suggested the early diagnostic value 
of a test to detect IgA antibodies to HIV in infants.  
      In contrast, the HIV antibody test now in routine use, which tests for a 
different class of antibodies, cannot reliably detect HIV infection in infants 
younger that 12 to 15 months of age.  
      "This study demonstrates the  promise  of  the  IgA  antibody  test  for 
detecting  HIV  in infants many months before the blood tests currently used," 
said Anthony S.  Fauci,  M.D.,  Director of NIAID.  "Early  diagnosis  of  HIV 
infection  in infants identifies those likely to develop HIV-related illnesses 
and provides information crucial to the  management  and  treatment  of  these 
children." 
      The World Health Organization estimates that,  worldwide, over 3 million 
women of reproductive age are infected with  HIV.  The  chance  that  an  HIV-
infected  mother will pass on the virus to her fetus is from 13 to 45 percent, 
according to published studies.  Internationally,  it is  estimated  that  one 
million children acquired HIV before or during birth in 1990 alone.  
      Through October 31, 1991, 3,372 children were diagnosed with AIDS in the 
United   States;   1,798   of  them  have  died.   Researchers  estimate  that 
approximately 7,000 to 10,000 additional children in  the  United  States  are 
currently infected with HIV.  
      "Almost  half  of  HIV-infected  children  develop  HIV-related symptoms 
within the first year of life, with nearly 70 percent developing AIDS by their 
second birthday," said lead author Thomas C.  Quinn M.D.,  Senior Investigator 
at NIAID,  and Professor of Medicine and International Health at Johns Hopkins 
University.  "It is crucial that therapy be initiated as soon as  an  accurate 
diagnosis of HIV infection can be made." 
      The  HIV  antibody  tests  currently  in  use are designed to detect IgG 
antibodies,  proteins secreted  by  white  blood  cells  in  response  to  HIV 
infection.  During pregnancy, IgG antibodies produced by an HIV-infected woman 
cross  the  placenta  to her fetus;  after birth,  the maternal IgG antibodies 
persist in the infant's bloodstream for 12 to 15 months.  
      If an infant is infected with HIV before or during birth, he or she will 
also produce IgG antibodies to HIV.  However,  the current tests are unable to 
distinguish between the mother's IgG,  and the infant's IgG.  Thus,  for 12 to 
15 months,  it is often unclear to physicians whether the infant  is  actually 
infected, or merely carrying maternal antibodies to HIV.  
      "For  the  physician,  this  has presented a quandary," said Dr.  Quinn.  
"Should anti-HIV therapy and preventive therapy for opportunistic  infections, 
with  their  known  benefits,  be started?  Some children will benefit,  but a 
majority of infants are not infected and may suffer the potential site effects 
of therapies unnecessarily.  The IgA antibody  test  will  help  resolve  this 
situation." 
      Unlike  IgA antibodies do not travel across the placenta;  thus,  a test 
for IgA antibodies reveals  actual  infection  because  any  IgA  presents  is 
definitely not of maternal origin.  
      In  the  current  study,  Dr.  Quinn  and his colleagues evaluated blood 
samples from 116 children born to HIV-infected women  and  followed  at  Johns 
Hopkins  University  Hospital  in  Baltimore,  and  162  children born to HIV-
infected women in Port-au-Prince,  Haiti.  As controls,  42 children  born  to 
uninfected women in Port-au-Prince were evaluated.  
      IgA  tests  were  performed on blood samples from babies at ages ranging 
from 1 day to 6 months and older.  HIV status was later confirmed by  clinical 
assessment and routine IgG antibody tests after 15 months of age.  
      A  total  of  47  children--34  U.S.  and 13 Haitian--were HIV infected.  
 
Among,  the U.S.  children,  32 (94.1 percent) of 34 children  who  were  IgA-
positive were later confirmed to be HIV-positive.  
      When  the  investigators  confirmed  and  analyzed  the  results for all 
children who were 3 months of age or older,  they found only 1 false  positive 
and 4 false negative results out of a total of 498 blood samples.  
      When  the investigators analyzed the IgA blood tests by age,  they found 
that 1 out of 6 HIV-infected children tested in the first month  of  life  was 
IgA-positive  (17  percent).  At  3 months,  6 of 9 HIV-infected children were 
IgA-positive 66.7 percent),  and at 6 months,  15 of 16 HIV-infected  children 
were  IgA positive (93.8 percent).  After 6 months of age,  all of the samples 
drawn from 45 infected children were IgA-positive.  The other 2 of the 47 HIV-
infected children were lost to followup.  





      "We found that IgA antibodies are frequently  absent  during  the  first 
weeks  of  life in children born to HIV-infected women," Dr.  Quinn said.  "In 
fact,  we found IgA in only 1 out of 5 babies we sampled in their first  week, 
but it's also important to note that we had very few samples from infants that 
young.  Most  of the HIV-infected babies that we studied developed IgA between 
3 and 6 months of age." 
      Dr.  Quinn said that further studies should  include  analysis  of  more 
blood samples obtained from infants between birth and 3 months of age, to more 
accurately  assess  the  ability  of the IgA test to predict infection in very 
young infants,  and to provide  more  information  about  the  timing  of  HIV 
transmission from mother to infant.  
      Alternative  methods  of  diagnosing  HIV  have  notable  disadvantages.  
 
Laboratory culture of the virus in cells and amplification  of  viral  DNA  by 
polymerase chain reaction (PCR) are not completely standardized;  in addition, 
they are expensive  and  involve  sophisticated  technological  expertise  and 
equipment,  barriers  to their use in developing countries.  In contrast,  the 
IGA test is a relatively simple and inexpensive blood test that can be readily 
performed in many laboratories worldwide.  
      Collaborators in the study included Thomas C.  Quinn, M.D.,  and Richard 
L.  Kline,  M.S.,  National  Institute  of Allergy and Infectious Diseases and 
Johns Hopkins University;  Reginald Boulous, M.D.,  Center for Development and 
Health,  Port au Prince,  Haiti;  and Neal Halsey,  M.D.,  Nancy Hutton, M.D., 
Andrea Ruff, M.D., Arlene Butz, R.N., Sc.D., and John F.  Modlin, M.D., all of 
Johns Hopkins University.

