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Rabies vaccination in pregnancy
Communications
synechiae. The value of hysteroscopy is amply demonstrated in this patient. It ruled out the presence of uterine synechiae and confirmed the presence of bones. Curettage alone could have easily missed all the bones that were partially embedded near the fundus because we encountered difficulty in grasping the bones even with the ovum forceps after knowing the location ofthe bones. Hysteroscopy enabled visualization of the bones and their location. We postulate that the presence of the bones prevented pregnancy by acting as a uterine synechia or an IUD. In this respect, the presence of an IUD has been shown to increase significantly the prostaglandin content of the endometrium in women’ and both the endometrial content and uterine venous blood levels of prostaglandin Fta (PGF,,) of the IUD-bearing uterine horn of the ewe.? In the ewe, the endometrial PGF,, content of the IUD-bearing area is significantly higher rhan that of the intervening endometrial surfce of the uterine horn fitted \vith several IUDS.~ Thus, elevation ot’ the local endometrial PGFLa content probably pre\‘ents implantation. In our patient, we are tempted to conclude that the presence of the bones near the tnnda1 region elevated the endometrial PGF,, concentration of the tundal region, a common site of blastocyst implantation, and thus rendered her infertile.
1. Hillier, K., and Kasonde, J. M.: Prostaglandin E and F concentrations in human endometrium after insertion of intrauterine contraceptive device, Lancet 1: 15, 1977. 2. Spillman, C. H., and buby, R. T.: Prostaglandin mediated luteolytic effect of an intrauterine device in sheep, Prostaglandins 2:159, 1972.
MICHAEL GAIL A. RUDOLPH
M. R.. a 22-year-old Caucasian woman, gravida 3. para I, whose estimated date of confinement was August 18, 1980, by date of last menstrual period and ultrasound. was first seen at The University of Iowa Hospitals and Clinics on July 7, 1980. for treatment of a bat bite incurred on July -1, 1980. Attempts to capture the animal were unsuccessful. The pregnancy previously had been uncomplicated. Her medical history was remarkable only for an exploratory laparotom) in 1977 for a tUbal ectopic pregnancy and a primary cesarean section in 197X tor failure to progress in labor. Physical examination revealed an obese white woman whose uterus was compatible with 3-I weeks’ gestation. Two 1 .!I mm puncture wounds were present 5 mm apart on the left heel. These were minimally tender and nonerythematous. She was given 20 IUlkg of human rabies immunoglobulin. half locally
in the left
heel
and
W. VARNER, McGUINNESS,
P. GALASK,
M.D.
Departments of Obstetrics and Gynecology lJniversit)l of Iowa Hospitals and Clinics,
injections
and Pediatrics, The Iowa City, Iowa
Reprint requests: Dr. Michael W. Varner, Department of Obstetrics and Gynecology, The University of Iowa Hospitals and Clinics. Iowa City, Iowa 52242. 1982 The C.V.
left
arm.
She also re-
of
human
diploid
cell
rabies
vaccine
on
the
sub-
sequent third, seventh, fourteenth, and twenty-eighth days. However, she returned two days folknving the initial injection complaining of myalgia, anorexia, and tatigue. without evidence of premature labor or decreased fetal activity. She without incident and was given 1 ml rabies vaccine on July 10. 1980. She
again returned two days following of ill-dehned abdominal discomfort tions, bleeding, ruptured urologic complaints. Vital
the injection cotnplaining
\vithout specific contracmembranes, gastrointestinal or signs again remained stable and she injection \vas administered July 14,
was discharged, The third 1980, and the fourth injection was given on July 21, 1980. On July 23, 1980. she again reported similar symptoms. She received the final injection on August 4. 1980, and two days later again developed the same abdominal discomtort. anorexia, and fatigue.
mother
M.D.
HUI\IAN DIPLOID CELL rabies vaccine was approved for use in the United States on June 9, 1980, and has largely replaced duck embryo vaccine because of higher inducible antibody levels obtained with fewer injections and fewer adverse reactions. While few humans die of rabies, it has been estimated that as many as 30,000 people annually require rabies prophylaxis in the United States. This popula-
0002.9378/8?/140717+02$00.20/0~
in the
admitted
on August
10, 19X0, and
underwent
an uncomplicated low-transverse cesarean section under epidural anesthesia. The 2,850 gram female infant had Apgar scores of 7 and 9 at 1 and 5 minutes, respectively. Both
M.D.
M.S.,
half
ceived 1 ml of Merieux human diploid cell rabies vaccine in the right arm and was instructed to return for repeat I ml
She was next
Rabies vaccination in pregnancy
717
tion would be expected to involve reproductive-aged women and thus would prompt concern regarding the safety of this procedure in pregnancy. We wish to report the first case of human diploid cell rabies vaccination associated with pregnancy.
was observed overnight of human diploid cell
REFERENCES
in brief
Mosby Co.
and
infant
did
well and
were
discharged
on the fifth
postoperative day. Both mother and daughter have done well for one year following delivery. The child has showy normal developmental progress through the first year of life. Serum spectmens for rabie+neutraliLing antibodies \verc dralvn during the course of \raccination, at the time of delivery. and at intervals in the year following delivery. These are demonstrated in Table I. Rabies-neutralizing antibody assays were performed by the Centers for Disease Control by means of the rapid fluorescent focus-inhibition test. Human diploid cell rabies vaccine represents a significant improvement in the prevention of human rabies. Not only can the number of injections used for postexposure treatment be reduced from 14 to 23 to five, but also this new vaccine is more immunogenic, causes very early antibody induction, and causes substantially fewer side effects. This vaccine induces both IgM and IgG antibodies.
718
Communications
in brief
I. Titers obtained by rapid fluorescent focus-inhibition test in mother and inf’anr ftillowing vaccination with human diploid cell rabies vaccine Table
7‘lVW
7‘/trr irr M~l/lPl
Day 0 Dav 7 Da\, 14 Da;, 2X Deliver! Three weeks Two months Six months one vear
1 :.‘I) 11 :30 > I :.io > I :io I:16
I‘itc,, 1), /t/f//t/l
> I :.:,o I :G 1:x 1: I(i
IgC; antibody titers correlate w,ell with neutraliring. and hemagglutination-inhibition complement-fixing, assays but IgM antibodies do not. This vaccine also induces an early, strong T-cell-mediated response. There are se\,eral reports documenting postexposure rabies prophylaxis with duck embryo vaccine during pregnancy.‘. p However, only one published mention ot human diploid cell rabies vaccine administration during pregnancy exists and that communication fails to report the eventual outcome of’ the pregnant) .‘( Transplacental transmission of rabies virus has been reported in some animals. The \,irus also has been inplicated as a teratogen in chick embryos and l~umal~s.’ although several other reports ha\,e been unable to show evidence of viral transf’er across the human placenta.‘. “ One published report’ has documented apparent passive transplacental transfer ot‘ antirabies antibody tollowing postexposure vaccination with duck embrvo vaccine in the third trimester. Neither mothel nor inf’:rnt suifered any reported secluelac. This case suggests that the high antirabies antihod) titers fo~~nd in the cord and neonatal serum represent passive transplacental transfer, as indicated b!- return to nondetectable levels in the serum of the one-\ ear-okI infant despite the presence of’ persistent maternal liters. Specific neonatal and infant lymphocyte f’unction was not evaluated in this case. However, possible stimulation bv transplacentally acquired attenuated virus must remain a potential consideration. Although this patient did experience abdominal discomf’ort, anorexia, and fatigue following human diploid cell rabies vaccine in.jections, these side effects are not considered serious and hale been reported lvith previous srudies. It must be emphasized thar the successf’111 outcome of’ this case does not prove that human diploid cell rabies vaccine is without risk in pregnancy. However, given the near 100% death rate with rabies, the minimal incidence of serious vaccine-related side effects. and the high degree of‘efficacy of’human diploid cell rabies vaccine in preventing human rabies, it would appeal that human cliploid cell rabies vaccine should be
used for postexposure pregnancy.
rabies
prophylaxis
in humat
The technical assistance of Dr. John Sumner, Viral Diseases Division Laboratory, Centers for Disease Control, i\tlanta. Georgia, is acknowledged. REFERENCES 1. (&es. \2’.: Treatment oti rabies estxxare during pregnancy. Obstet. G)necol. 44:893. 197-j. ‘L. Sncnce. M. R.. Davidson. D. E.. Dill. C S., Bounthai, I’.. and Sagartr. ,J. W.: Rabies exposurr during pregnanq, Afv. J. <)BSTET. (;YNECOL. 123:655. 197.5. 3. Kleitmann. W., Domrcs, B., and Cox. J. H.: Rabies postexposure treatment and side-et’fecta in man using HDC (MRC 5) vaccine. Dev. Biol. Stand. 40:109. 197X. 4. Jelesic. %.: liongenitale Missbildungen und das tollwlt\,irus. .Arch. Hyg. Bakteriol. 142:8, 195X.
Use of magnesium sulfate in premature labor that fail-s to respond to ,&mimetic drugs (;CILLERMO \‘ALEN%UELA, SL’SAS (:LINE. R.N.
.M.D.
.\s I NFI:SION 01 p-mimetic drugs c)r magnesium sulfare’ tails to stop contractions in approximately 20% of patients in premature labor. At the Medical Center Hospital. pa’ients complaining of uterine contractions between Y-4 and :14 weeks are evaluated as described prc\ iousl\-.’ Those patients having t\\o or more contractions in IO minutes are admitted and receive .iOO ml of intravenous fluid rapidly and H mg of morphine inti-;imus~Lllarl~.. Patients \vho continue having contractions after 1 hour ot‘ observation xe placed on a regimen of’/%milnetic drug therapy as described pre\ i0us1y.~ Once c.ontractions stop, the ~wmw~ undergo sonography and manv have an amniocentesis perfin-med fi~rdeter~ninati~~nt~f.thelecithin/sphingo~n~elin (L/S) ratio. It‘ the L/S ratio indicates fetal lung tnaturity. p-mimetic drugs are stopped. During the past year, fi1.e patients failed to respond to p-mimetic drugs and were treated \\ith magnesium sulfate. This was given as an intravenous infusion of I! to 4 gm of’ magnesium sulfate fill- L1 minutes f’ollowed by an intravenous inf’usion of. 2 gmihr. Usually an increase in urinary output \\as noticed when the pmimetic drugs were discontinued; therelijre, to mainReprint requests: Guillermo Valenzuela. M.D., The Uuiwrsity of Texas Health Science Center, 7703 Floyd Curl Dr., Department ofObstetrics and Gynecology. San Alltonio, Texas 78284.
synechiae. The value of hysteroscopy is amply demonstrated in this patient. It ruled out the presence of uterine synechiae and confirmed the presence of bones. Curettage alone could have easily missed all the bones that were partially embedded near the fundus because we encountered difficulty in grasping the bones even with the ovum forceps after knowing the location ofthe bones. Hysteroscopy enabled visualization of the bones and their location. We postulate that the presence of the bones prevented pregnancy by acting as a uterine synechia or an IUD. In this respect, the presence of an IUD has been shown to increase significantly the prostaglandin content of the endometrium in women’ and both the endometrial content and uterine venous blood levels of prostaglandin Fta (PGF,,) of the IUD-bearing uterine horn of the ewe.? In the ewe, the endometrial PGF,, content of the IUD-bearing area is significantly higher rhan that of the intervening endometrial surfce of the uterine horn fitted \vith several IUDS.~ Thus, elevation ot’ the local endometrial PGFLa content probably pre\‘ents implantation. In our patient, we are tempted to conclude that the presence of the bones near the tnnda1 region elevated the endometrial PGF,, concentration of the tundal region, a common site of blastocyst implantation, and thus rendered her infertile.
1. Hillier, K., and Kasonde, J. M.: Prostaglandin E and F concentrations in human endometrium after insertion of intrauterine contraceptive device, Lancet 1: 15, 1977. 2. Spillman, C. H., and buby, R. T.: Prostaglandin mediated luteolytic effect of an intrauterine device in sheep, Prostaglandins 2:159, 1972.
MICHAEL GAIL A. RUDOLPH
M. R.. a 22-year-old Caucasian woman, gravida 3. para I, whose estimated date of confinement was August 18, 1980, by date of last menstrual period and ultrasound. was first seen at The University of Iowa Hospitals and Clinics on July 7, 1980. for treatment of a bat bite incurred on July -1, 1980. Attempts to capture the animal were unsuccessful. The pregnancy previously had been uncomplicated. Her medical history was remarkable only for an exploratory laparotom) in 1977 for a tUbal ectopic pregnancy and a primary cesarean section in 197X tor failure to progress in labor. Physical examination revealed an obese white woman whose uterus was compatible with 3-I weeks’ gestation. Two 1 .!I mm puncture wounds were present 5 mm apart on the left heel. These were minimally tender and nonerythematous. She was given 20 IUlkg of human rabies immunoglobulin. half locally
in the left
heel
and
W. VARNER, McGUINNESS,
P. GALASK,
M.D.
Departments of Obstetrics and Gynecology lJniversit)l of Iowa Hospitals and Clinics,
injections
and Pediatrics, The Iowa City, Iowa
Reprint requests: Dr. Michael W. Varner, Department of Obstetrics and Gynecology, The University of Iowa Hospitals and Clinics. Iowa City, Iowa 52242. 1982 The C.V.
left
arm.
She also re-
of
human
diploid
cell
rabies
vaccine
on
the
sub-
sequent third, seventh, fourteenth, and twenty-eighth days. However, she returned two days folknving the initial injection complaining of myalgia, anorexia, and tatigue. without evidence of premature labor or decreased fetal activity. She without incident and was given 1 ml rabies vaccine on July 10. 1980. She
again returned two days following of ill-dehned abdominal discomfort tions, bleeding, ruptured urologic complaints. Vital
the injection cotnplaining
\vithout specific contracmembranes, gastrointestinal or signs again remained stable and she injection \vas administered July 14,
was discharged, The third 1980, and the fourth injection was given on July 21, 1980. On July 23, 1980. she again reported similar symptoms. She received the final injection on August 4. 1980, and two days later again developed the same abdominal discomtort. anorexia, and fatigue.
mother
M.D.
HUI\IAN DIPLOID CELL rabies vaccine was approved for use in the United States on June 9, 1980, and has largely replaced duck embryo vaccine because of higher inducible antibody levels obtained with fewer injections and fewer adverse reactions. While few humans die of rabies, it has been estimated that as many as 30,000 people annually require rabies prophylaxis in the United States. This popula-
0002.9378/8?/140717+02$00.20/0~
in the
admitted
on August
10, 19X0, and
underwent
an uncomplicated low-transverse cesarean section under epidural anesthesia. The 2,850 gram female infant had Apgar scores of 7 and 9 at 1 and 5 minutes, respectively. Both
M.D.
M.S.,
half
ceived 1 ml of Merieux human diploid cell rabies vaccine in the right arm and was instructed to return for repeat I ml
She was next
Rabies vaccination in pregnancy
717
tion would be expected to involve reproductive-aged women and thus would prompt concern regarding the safety of this procedure in pregnancy. We wish to report the first case of human diploid cell rabies vaccination associated with pregnancy.
was observed overnight of human diploid cell
REFERENCES
in brief
Mosby Co.
and
infant
did
well and
were
discharged
on the fifth
postoperative day. Both mother and daughter have done well for one year following delivery. The child has showy normal developmental progress through the first year of life. Serum spectmens for rabie+neutraliLing antibodies \verc dralvn during the course of \raccination, at the time of delivery. and at intervals in the year following delivery. These are demonstrated in Table I. Rabies-neutralizing antibody assays were performed by the Centers for Disease Control by means of the rapid fluorescent focus-inhibition test. Human diploid cell rabies vaccine represents a significant improvement in the prevention of human rabies. Not only can the number of injections used for postexposure treatment be reduced from 14 to 23 to five, but also this new vaccine is more immunogenic, causes very early antibody induction, and causes substantially fewer side effects. This vaccine induces both IgM and IgG antibodies.
718
Communications
in brief
I. Titers obtained by rapid fluorescent focus-inhibition test in mother and inf’anr ftillowing vaccination with human diploid cell rabies vaccine Table
7‘lVW
7‘/trr irr M~l/lPl
Day 0 Dav 7 Da\, 14 Da;, 2X Deliver! Three weeks Two months Six months one vear
I‘itc,, 1), /t/f//t/l
> I :.:,o I :G 1:x 1: I(i
IgC; antibody titers correlate w,ell with neutraliring. and hemagglutination-inhibition complement-fixing, assays but IgM antibodies do not. This vaccine also induces an early, strong T-cell-mediated response. There are se\,eral reports documenting postexposure rabies prophylaxis with duck embryo vaccine during pregnancy.‘. p However, only one published mention ot human diploid cell rabies vaccine administration during pregnancy exists and that communication fails to report the eventual outcome of’ the pregnant) .‘( Transplacental transmission of rabies virus has been reported in some animals. The \,irus also has been inplicated as a teratogen in chick embryos and l~umal~s.’ although several other reports ha\,e been unable to show evidence of viral transf’er across the human placenta.‘. “ One published report’ has documented apparent passive transplacental transfer ot‘ antirabies antibody tollowing postexposure vaccination with duck embrvo vaccine in the third trimester. Neither mothel nor inf’:rnt suifered any reported secluelac. This case suggests that the high antirabies antihod) titers fo~~nd in the cord and neonatal serum represent passive transplacental transfer, as indicated b!- return to nondetectable levels in the serum of the one-\ ear-okI infant despite the presence of’ persistent maternal liters. Specific neonatal and infant lymphocyte f’unction was not evaluated in this case. However, possible stimulation bv transplacentally acquired attenuated virus must remain a potential consideration. Although this patient did experience abdominal discomf’ort, anorexia, and fatigue following human diploid cell rabies vaccine in.jections, these side effects are not considered serious and hale been reported lvith previous srudies. It must be emphasized thar the successf’111 outcome of’ this case does not prove that human diploid cell rabies vaccine is without risk in pregnancy. However, given the near 100% death rate with rabies, the minimal incidence of serious vaccine-related side effects. and the high degree of‘efficacy of’human diploid cell rabies vaccine in preventing human rabies, it would appeal that human cliploid cell rabies vaccine should be
used for postexposure pregnancy.
rabies
prophylaxis
in humat
The technical assistance of Dr. John Sumner, Viral Diseases Division Laboratory, Centers for Disease Control, i\tlanta. Georgia, is acknowledged. REFERENCES 1. (&es. \2’.: Treatment oti rabies estxxare during pregnancy. Obstet. G)necol. 44:893. 197-j. ‘L. Sncnce. M. R.. Davidson. D. E.. Dill. C S., Bounthai, I’.. and Sagartr. ,J. W.: Rabies exposurr during pregnanq, Afv. J. <)BSTET. (;YNECOL. 123:655. 197.5. 3. Kleitmann. W., Domrcs, B., and Cox. J. H.: Rabies postexposure treatment and side-et’fecta in man using HDC (MRC 5) vaccine. Dev. Biol. Stand. 40:109. 197X. 4. Jelesic. %.: liongenitale Missbildungen und das tollwlt\,irus. .Arch. Hyg. Bakteriol. 142:8, 195X.
Use of magnesium sulfate in premature labor that fail-s to respond to ,&mimetic drugs (;CILLERMO \‘ALEN%UELA, SL’SAS (:LINE. R.N.
.M.D.
.\s I NFI:SION 01 p-mimetic drugs c)r magnesium sulfare’ tails to stop contractions in approximately 20% of patients in premature labor. At the Medical Center Hospital. pa’ients complaining of uterine contractions between Y-4 and :14 weeks are evaluated as described prc\ iousl\-.’ Those patients having t\\o or more contractions in IO minutes are admitted and receive .iOO ml of intravenous fluid rapidly and H mg of morphine inti-;imus~Lllarl~.. Patients \vho continue having contractions after 1 hour ot‘ observation xe placed on a regimen of’/%milnetic drug therapy as described pre\ i0us1y.~ Once c.ontractions stop, the ~wmw~ undergo sonography and manv have an amniocentesis perfin-med fi~rdeter~ninati~~nt~f.thelecithin/sphingo~n~elin (L/S) ratio. It‘ the L/S ratio indicates fetal lung tnaturity. p-mimetic drugs are stopped. During the past year, fi1.e patients failed to respond to p-mimetic drugs and were treated \\ith magnesium sulfate. This was given as an intravenous infusion of I! to 4 gm of’ magnesium sulfate fill- L1 minutes f’ollowed by an intravenous inf’usion of. 2 gmihr. Usually an increase in urinary output \\as noticed when the pmimetic drugs were discontinued; therelijre, to mainReprint requests: Guillermo Valenzuela. M.D., The Uuiwrsity of Texas Health Science Center, 7703 Floyd Curl Dr., Department ofObstetrics and Gynecology. San Alltonio, Texas 78284.