Rubella Reinfection A Case of Mistaken
Diagnosis
of
During Pregnancy
Congenital Rubella
Stella Biano, MD; William Cochran, MD; Kenneth L. Herrmann, MD; Anna D. Hall; Te-Wen \s=b\ A case
of subclinical rubella reinfec-
during pregnancy with serologic findings in the offspring initially led to an erroneous diagnosis of fetal infection. Laboratory diagnosis of congenital rubella infection, based on finding hemagglutination-inhibition (HI) activity in immunoglobulin M (IgM) fractions of newborn's serum after sucrose gradient fractionation, was questioned when apparent IgM-HI activity was to be probably due to nonspecific inhibitors, which resulted tion
from bacterial action on the \g=b\-lipoprotein in the serum. These findings emphasize some pitfalls encountered in arriving at a diagnosis based soley on serologic data. This case also illustrates the importance of keeping serum samples sterile when performing serologic tests. (Am J Dis Child 129:1353-1356, 1975)
reinfection is now recog¬ nized and acknowledged as a frequent occurrence in individuals vac¬ cinated following exposure to natural
Rubella
Received for publication Oct 2, 1974; accepted Dec 12. From the Boston Hospital for Women, Harvard Medical School, Boston (Drs Biano and Cochran), the Virology Division, Center for Disease Control, Atlanta (Dr. Herrmann and Ms Hall), and the Tufts-New England Medical Center, Boston (Dr Chang). Reprint requests to Boston Hospital for Women, 221 Longwood Ave, Boston, MA 02115
(Dr Biano).
rubella infections.1·2 Reinfection has also been documented in persons with histories and serologie evidence of previous natural rubella.11 It has been reported that reinfection occurs more frequently in persons with lower lev¬ els of rubella antibodies.4 Accuracy of the serologie tests employed to detect rubella antibodies is, therefore, crit¬ ical when attempting to differentiate primary infection from reinfection or when determining whether a signifi¬ cant titer change has taken place. The occurrence of nonspecific inhibition in the rubella hemagglutination-inhibition (HI) test could cause false-posi¬ tive results or erroneously elevated antibody titers that might lead to the misinterpretation of test results. Six cases of presumed rubella rein¬ fection during pregnancy have been previously reported.3" Two of these reported reinfections resulted in in¬ trauterine involvement, one with placentitis,'1 and the other with positive virus isolation from the products of conception.5 Both pregnancies were terminated by abortion. Since then, there have been some doubts as to whether these cases had primary in¬ fection, rather than reinfection.3 Such doubts must be satisfactorily an¬ swered before the risk of fetal in¬ volvement resulting from maternal reinfection can be clearly defined.
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Chang,
MD
This report describes an additional of maternal rubella reinfection with previously undescribed nonspe¬ cific serologie findings in the newborn offspring, which resulted in an erro¬ neous initial laboratory diagnosis of congenital rubella infection. case
MATERIALS AND METHODS Rubella
hemagglutination-inhibition
(HI) antibody was determined by the stan¬
dard rubella HI procedure from the Center for Disease Control; there were modifica¬ tions using a heparin-manganous chloride mixture and sodium carbonate for the re¬ moval of nonspecific inhibitors.1"·" The se¬
immunoglobulins were separated by gradient ultracentrifugation,12 and specific rubella IgM and IgG antibodies de¬ termined by the above HI technique. The serum fractions were also analyzed for specific IgM and IgG content and for ru¬ bella precipitins using immunoelectrophoresis" and double-diffusion agar gel precipitation methods.14 Rubella comple¬ ment-fixing (CF) antibody titers were de¬ termined by the standardized complement
rum
sucrose
fixation method.15 Immunofluorescent anti¬ was detected by the indirect fluores¬ cent antibody technique using rubellavirus-infected Vero cells overlaid with 1:4 dilution of serum and stained with fluorescein-conjugated antihuman globulin.1" Ru¬ bella virus isolation and neutralizing anti¬ body assay were both carried out in primary African green monkey cell cul¬ tures using the enterovirus interference
body
Rubella Antibody
Response and Virus Isolation
Hemaggluti nation-Inhibiting Antibody
Mother 18-weeks' gestation At delivery Infant At birth* Age 1 mo Age 3 mo *
ComplementFixing Antibody
Fluorescent
IgM
Neutralizing Antibody
Diagnosis
of
During Pregnancy
Congenital Rubella
Stella Biano, MD; William Cochran, MD; Kenneth L. Herrmann, MD; Anna D. Hall; Te-Wen \s=b\ A case
of subclinical rubella reinfec-
during pregnancy with serologic findings in the offspring initially led to an erroneous diagnosis of fetal infection. Laboratory diagnosis of congenital rubella infection, based on finding hemagglutination-inhibition (HI) activity in immunoglobulin M (IgM) fractions of newborn's serum after sucrose gradient fractionation, was questioned when apparent IgM-HI activity was to be probably due to nonspecific inhibitors, which resulted tion
from bacterial action on the \g=b\-lipoprotein in the serum. These findings emphasize some pitfalls encountered in arriving at a diagnosis based soley on serologic data. This case also illustrates the importance of keeping serum samples sterile when performing serologic tests. (Am J Dis Child 129:1353-1356, 1975)
reinfection is now recog¬ nized and acknowledged as a frequent occurrence in individuals vac¬ cinated following exposure to natural
Rubella
Received for publication Oct 2, 1974; accepted Dec 12. From the Boston Hospital for Women, Harvard Medical School, Boston (Drs Biano and Cochran), the Virology Division, Center for Disease Control, Atlanta (Dr. Herrmann and Ms Hall), and the Tufts-New England Medical Center, Boston (Dr Chang). Reprint requests to Boston Hospital for Women, 221 Longwood Ave, Boston, MA 02115
(Dr Biano).
rubella infections.1·2 Reinfection has also been documented in persons with histories and serologie evidence of previous natural rubella.11 It has been reported that reinfection occurs more frequently in persons with lower lev¬ els of rubella antibodies.4 Accuracy of the serologie tests employed to detect rubella antibodies is, therefore, crit¬ ical when attempting to differentiate primary infection from reinfection or when determining whether a signifi¬ cant titer change has taken place. The occurrence of nonspecific inhibition in the rubella hemagglutination-inhibition (HI) test could cause false-posi¬ tive results or erroneously elevated antibody titers that might lead to the misinterpretation of test results. Six cases of presumed rubella rein¬ fection during pregnancy have been previously reported.3" Two of these reported reinfections resulted in in¬ trauterine involvement, one with placentitis,'1 and the other with positive virus isolation from the products of conception.5 Both pregnancies were terminated by abortion. Since then, there have been some doubts as to whether these cases had primary in¬ fection, rather than reinfection.3 Such doubts must be satisfactorily an¬ swered before the risk of fetal in¬ volvement resulting from maternal reinfection can be clearly defined.
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 06/21/2015
Chang,
MD
This report describes an additional of maternal rubella reinfection with previously undescribed nonspe¬ cific serologie findings in the newborn offspring, which resulted in an erro¬ neous initial laboratory diagnosis of congenital rubella infection. case
MATERIALS AND METHODS Rubella
hemagglutination-inhibition
(HI) antibody was determined by the stan¬
dard rubella HI procedure from the Center for Disease Control; there were modifica¬ tions using a heparin-manganous chloride mixture and sodium carbonate for the re¬ moval of nonspecific inhibitors.1"·" The se¬
immunoglobulins were separated by gradient ultracentrifugation,12 and specific rubella IgM and IgG antibodies de¬ termined by the above HI technique. The serum fractions were also analyzed for specific IgM and IgG content and for ru¬ bella precipitins using immunoelectrophoresis" and double-diffusion agar gel precipitation methods.14 Rubella comple¬ ment-fixing (CF) antibody titers were de¬ termined by the standardized complement
rum
sucrose
fixation method.15 Immunofluorescent anti¬ was detected by the indirect fluores¬ cent antibody technique using rubellavirus-infected Vero cells overlaid with 1:4 dilution of serum and stained with fluorescein-conjugated antihuman globulin.1" Ru¬ bella virus isolation and neutralizing anti¬ body assay were both carried out in primary African green monkey cell cul¬ tures using the enterovirus interference
body
Rubella Antibody
Response and Virus Isolation
Hemaggluti nation-Inhibiting Antibody
Mother 18-weeks' gestation At delivery Infant At birth* Age 1 mo Age 3 mo *
ComplementFixing Antibody
Fluorescent
IgM
Neutralizing Antibody
