Guidelines on the management of, and exposure to, rash
illness in pregnancy (including consideration of relevant antibody screening
programmes in pregnancy).
Morgan-Capner P, Crowcroft NS; PHLS Joint Working Party of the Advisory
Committees of Virology and Vaccines and Immunisation.
Preston Public Health Laboratory, Royal Preston Hospital, PO Box 202, Sharoe
Green Lane, Fulwood, Preston, Lancashire PR2 9HG.
peter.morgan-capner@csr-tr.nwest.nhs.uk
These guidelines, produced by the Public Health Laboratory Service (PHLS) aim
to help decision making in the investigation and management of pregnant women
who have 'a rash compatible with a systemic viral illness', or who have
contact with a person with such an illness. They address particularly rubella,
parvovirus B19, and varicella-zoster virus infection, but consider other
infective causes of rash illness in the United Kingdom. The guidelines give
the magnitude and degrees of risk to the fetus in terms of outcomes for the
gestation at which maternal infection occurs. Recent changes in epidemiology
and management lead to the following specific advice, which both updates and
re-affirms established guidelines. All pregnant women with a non-vesicular
rash illness should be investigated simultaneously for rubella and parvovirus
B19 infection. All pregnant women who have had significant contact with a
person suffering from a non-vesicular illness should be investigated for
asymptomatic parvovirus B19 infection, and for
asymptomatic rubella infection
unless there is satisfactory evidence of past rubella infection (vaccine or
natural infection). A significant contact is defined as being in the same room
for over 15 minutes, or face-to-face contact. Specific investigation to detect
asymptomatic rubella reinfection is not advised.
It is essential to confirm by adequate
laboratory investigation all cases of possible rubella and parvovirus B19
infection in pregnancy. Management of proven rubella in pregnancy
should be based on established risks of adverse outcome. Women with proven
parvovirus B19 infection in the first 20 weeks of pregnancy should be followed
by regular, ultrasound scanning, and referred to Regional Units of Fetal
Medicine if hydrops fetalis is detected. Parvovirus B19 antibody screening in
pregnancy is not advised, and consensus has been reached on the procedures to
be followed for rubella antibody screening, including the concentration of
antibody that reflects past infection. Oral antiviral treatment (aciclovir) is
advised with informed consent for pregnant women who present within 24 hours
of onset of varicella. Referral to hospital and intravenous antiviral
treatment is indicated for pregnant women with complications and/or risk
factors, or whose illness continues for six days or more. Pregnant women
exposed to varicella or herpes zoster can be reassured as to their protection
if they themselves have a history of varicella or herpes zoster. If this
history is uncertain or not known, susceptibility should be tested, and
varicellazoster immunoglobulin (VZIG) offered to those found susceptible if
within 10 days of first exposure. Infants whose mothers develop varicella 7
days before to 7 days after delivery should be given VZIG, and aciclovir if
onset was 4 days before to 2 days after delivery.
Rubella is a viral disease that
usually presents as a mild febrile rash illness in adults and children; however,
20%--50% of infected persons are asymptomatic.
Service de pediatrie generale Hopital Saint-Vincent-de-Paul, Paris.
Measles is an acute disease characterized by fever, cough, conjunctivitis,
erythematous maculopapular rash and pathognomonic enanthem. Vaccination had
resulted in decrease of complications and mortality. But vaccination coverage
in France is low, about 80%: the virus is always circulating and outbreaks in
teenagers are possible. The recommendation of a booster dose at age eleven
will contribute to reduce the incidence of the disease.
Rubella is asymptomatic in 30 to 50%
of infected children. There is a risk of transmission to pregnant women
with negative serology. Reduction of virus circulation and immunization of
young girls will result in decrease of the congenital rubella syndrome (65
cases/year in France). A vaccine booster dose at eleven in all children,
combined with measles immunization, is necessary.
Immune response to measles, mumps & rubella vaccine at 9,
12 & 15 months of age.
Singh R, John TJ, Cherian T, Raghupathy P.
Department of Child Health, Christian Medical College & Hospital, Vellore.
Seroconversion rates to measles, mumps and rubella (MMR) in children given MMR
vaccine at 9, 12 and 15 months of age were assessed so as to recommend the
optimum age for vaccination. A total of 164 infants were recruited, of whom
123 completed the study. Sera were tested pre-immunization and 4 wk after MMR
vaccine, for the presence and titres of antibodies by the haemagglutination
inhibition (HI) test and by enzyme-linked immunosorbant assay (ELISA). The
pre-immunization results showed that levels of maternal antibody detectable by
HI had disappeared by 9 months in all infants in the case of measles, but not
in the case of mumps or rubella.
Evidence for subclinical infection with the three viruses was found in 19 to
31 per cent of infants by 15 months of age. The responses to measles
antigen by both HI test and ELISA were better (> 95%) at 12 or 15 months than
at 9 months (80%). Vaccine failure was low at 12 or 15 months. The response to
mumps antigen by HI antigen was also higher (92%) at 12 months than at 9
months (75%). Vaccine failure was less frequent at 12 months than at 9 months.
The ELISA was found to be unreliable for mumps virus antibody testing. Rubella
vaccine evoked good seroresponse (> 92%) at 9, 12 and 15 months, both by HI
test and ELISA. Thus a better response to the MMR vaccine was obtained at or
after 12 months of age than earlier. Hence, a dose of MMR may be given
optimally at 12 months for children not previously immunized with measles
vaccine. For those already given measles vaccine, the MMR may be given at 12
or 15 months.
[Rubella epidemiology in military recruit schools]
[Article in German]
Matter L, Hohl P, Abelin T, Schopfer K.
SERUBDA-Projekt (Serologische Roteln-Untersuchung im biologischen Dienst der
Armee), Universitat Bern.
In 1986, at the start of their training, 6877 male recruits were screened for
the presence of anti-rubella IgG antibodies. 595 (9%) were seronegative. Of
the latter group, 475 (80%) were retested in the week prior to discharge.
During their four months of training, 113 (24%) exhibited seroconversion which
proved acquisition of a rubella virus infection during the period of service.
A clinical diagnosis of rubella was established in 15 (13%) of the persons
with seroconversion. Catarrhal symptoms were present in half of those
infected, whereas 41 (36%) did not report sick,
suggesting a subclinical course of
infection. Rubella is hardly a problem for the military in Switzerland.
However, outbreaks such as the ones reported may have implications for the
epidemiology of rubella in the general population, and hence should be taken
into account in the planning of programs attempting to eliminate rubella virus
infections.
Acute rubella infection in pregnant women in Delhi.
Kishore J, Broor S, Seth P.
Department of Microbiology, All India Institute of Medical Sciences, New
Delhi.
Serum samples of 17 pregnant women with suspected rubella who presented at the
Department of Microbiology, AIIMS, New Delhi, from March to May 1988 for
confirmation of diagnosis were tested for rubella haemagglutination inhibiting
(HAI) antibodies and rubella specific IgM antibodies by mu-capture ELISA. Ten
of the 17 women were diagnosed to have acute rubella infection as they showed
the presence of rubella specific IgM antibodies. Nine of these gave history of
fever and rash whereas one woman
remained asymptomatic. These observations suggest an increase in the
incidence of rubella infection in pregnant women from March to May 1988 in
Delhi.
[Evaluation of the immune status against the viruses of
measles, mumps, rubella, and hepatitis B in a cohort of students from the
province of Como]
[Article in Italian]
Fraizzoli G, Sesana BM.
Immunity status to measles, mumps, rubella and type B hepatitis (HB) viruses
was studied in a cohort of 83 teen-agers (13-14 years). The vaccination
against these agents is optional in Italy. Out of 83 subjects none had been
vaccinated against measles, mumps and HB viruses, while 31 had had rubella
vaccination. The percentage of seronegative adolescents was 2% for measles,
25% for mumps and 10% for rubella among unvaccinated teen-agers. These data
suggest that even adolescent could be a target for rubella and mumps
vaccination. On the contrary HBV does not appear to circulate extensively in
the early years of life, so there is no need to extend the vaccination outside
the risk groups. The presence of antibodies to measles, mumps and rubella
viruses correlated very well with the anamnestic recall referred by the
mothers. On the contrary for rubella
and mumps viruses there was a high proportion of seropositive
subjects with a negative history of disease. Therefore in the population under
study asymptomatic infections with rubella and mumps viruses should have been
rather frequent.
Rubella and cytomegalovirus (CMV) infections: laboratory
aspects of investigation of antenatal, congenital, persistent, and subclinical
infections.
Hossain A, Bakir TM.
Rubella specific IgM tests carried out on pregnant women with history of
rubella contact or rubella-like rash indicated the presence of rubella-IgM by
the second week after contact, persistence to 3-4 weeks followed by a decline
and non-detectability around 8-9 weeks and at delivery. Laboratory
investigation of cases of rubella infection in infants and children, including
clinically proven and suspected congenital rubella revealed distinct patterns
of combinations of positivity and negativity of IgM and IgG antibodies. Three
cases of persistence of rubella specific IgM antibodies with one even up to 3
years in congenital rubella and a case of CMV-IgM persistence in congenital
CMV are described. Rubella-IgM and CMV-IgM were detected in the serum of two
patients aged 12 years and 24 years with CMV mononucleosis.
Utilization of rubella-IgM/CMV-IgM
tests enabled the identification of four cases of subclinical rubella
and one of subclinical CMV in a pediatric population.
[Immune structure and rubella incidence in pregnant women
in Moscow]
[Article in Russian]
Vikhnovich EM, Stakhanova VM, Smorodintsev AA, Smorodinova IP, Visnitskii
NN.
The immune structure of the Moscow City population (mostly, pregnant women) in
relation to rubella virus antigen. Specific antihemagglutinins were found in
82%-93% of pregnant women, depending on their age.
Examination of sera from 207 pregnant
women who had contacts with rubella patients demonstrated clinically
manifest rubella verified serologically in 9.2%, and
asymptomatic form of rubella in 8.6%.
By an immunochemical method (treatment of sera with staphylococca reagent)
specific rubella IgM were found in 7 (100%) pregnant women who had experienced
clinically manifest rubella, and in 6 (14.3%) pregnant women with asymptomatic
rubella.
Fetal infection after maternal reinfection with rubella:
criteria for defining reinfection.
Best JM, Banatvala JE, Morgan-Capner P, Miller E.
Department of Virology, United Medical and Dental School, Guy's Hospital,
London.
Five cases of asymptomatic maternal
reinfection with rubella are described that occurred in England and Wales
during 1985-8 and resulted in intrauterine infection. The criteria for
diagnosing reinfection are described. In four cases the rubella contact was
with the woman's own children. Two women had therapeutic abortions, rubella
virus being recovered from the products of conception, and three were
delivered of infants with congenitally acquired disease. Though the risks
associated with maternal reinfection with rubella are very small and being
measured in a prospective study, it is hoped that the recently introduced
augmented programme of rubella vaccination will reduce rubella in the
community and therefore this small risk still further.
Ondokuzmayis Universitesi, Tip Fakultesi, Cocuk Sagligi ve Hastaliklari
Anabilim Dali.
Rubella infection in low birth weight infant was investigated with
enzyme-linked immunosorbent assay (ELISA). Thirty Low birth weight infants
were included in this study. Seropositive reaction (both Ig G and Ig M) was
found in four of the cases. One of the infants who showed hyperbilirubinemia,
sepsis and Low birth weight and another case who had tracheoesophageal fistula
died in three days. The other two cases which showed seropositive reaction are
being followed up as healthy children.
We reached the conclusion that Low birth weight may be related to asymptomatic
intrauterine rubella infection.
PMID: 3441222 [PubMed - indexed for MEDLINE]
How often is low birth weight viewed as a reason to
test for intrauterine rubella infection? - SM
Subclinical rubella
in pregnancy--occurrence and outcome.
Fogel A, Handsher R, Barnea B.
Between the years 1972 and 1979, 40,589 pregnant women were tested for rubella
antibodies following suspected illness or exposure, using hemagglutination-inhibition
(HI), complement fixation and staphylococcal absorption for determination of
specific immunoglobulin M (IgM). Recent primary infection was confirmed by
antibody rise in paired sera and/or the presence of specific IgM. Reinfection
was differentiated from primary asymptomatic rubella by absence of specific
IgM. Determination of neutralizing antibodies was also useful in confirming
reinfections. Clinical rubella was confirmed in 1,448 patients (3.6%). In
154 cases asymptomatic rubella infection was detected; 98 had primary
infection and 56 experienced reinfection.
In a selected group of 2,200 women
exposed to confirmed rubella, 6.8% had clinical rubella,
3.8% asymptomatic infection,
and in 7.1% the results were doubtful. Reinfection was detected in 12.4% of
265 women with initially low HI titers.
The prospective follow-up on pregnancy
outcome was available in 87 women with asymptomatic infection. Seven cases of
congenital rubella were detected in the group of primary infections,
while all 25 children born following reinfection were healthy.
Congenital rubella in Israel following the 1978-79 rubella
epidemic.
Brand N, Legum S, Saunders J, Fogel A.
We conducted a retrospective survey of children who were born with congenital
rubella syndrome (CR) resulting from a recent rubella epidemic. Sources of
information were hospital and laboratory records and data collected in an
active search for deaf children born following the epidemic and attending
rehabilitation centers for the deaf (Micha). Criteria for inclusion in the
survey were: 1) major clinical defects, and 2) one or more of the following
positive laboratory findings--virus isolation, presence of rubella-specific
IgM antibodies, or the presence of hemagglutination inhibition (HI) antibodies
in children beyond the age of 1 year. Excluded from the study were 28 children
with persistent HI antibodies, but without clinically detected defects. CR was
identified in 45, among them 43 with deafness. Other major defects were
psychomotor retardation, microcephaly, cataracts and heart defects. Transient
abnormalities included encephalitis, hepatosplenomegaly, jaundice,
thrombocytopenia, intrauterine grown retardation and failure to thrive.
Thirty-one mothers (70%) reported a
history of clinical rubella in pregnancy, the others having experienced
subclinical infection. Multiple defects were found in children born
following early gestational rubella (less than 2 months); abnormalities also
occurred as a consequence of rubella as late as the fifth month of gestation.
Asymptomatic rubella occurring in
mothers may be mild or clinically unapparent, yet cross the placental barrier.
The Baylor Group, through intensive clinical and virological studies, led the
country in the identification of an expanded CRS. The group concluded that
congenital heart, ear, eye, and CNS structural involvements were the result of
especially acute manifestations of ordinary congenital rubella. Neurological
disorders of the neonate previously ascribed to unknown etiologies were found
to be secondary to rubella encephalitis.
The ongoing occurrence of sub-acute
maternal rubella may therefore be responsible for innumerable cases of
neurological deficiencies in the neonate. Although immunization against
rubella was not effective until after the actual outbreak of the 1964
epidemic, the Baylor Group served to decelerate a health crisis through rapid,
coordinated efforts. Alerted to the possibility of a more diverse CRS, the
group prevented prolongation of the epidemic with appropriate treatment of
infected neonates.
The study is based upon primary rubella infections detected in a collection of
7,781 serum pairs from as many pregnant women out of a total number of about
12,500 in the Oslo area of Norway in 1974. In the spring of that year, a
rubella outbreak occurred. The results obtained on the serum pairs were
compared and supplemented with acute serodiagnostic data obtained from the
files of the virus laboratories, informations obtained from the mothers when
interviewed in 1976 and from the files of application for legal abortions.
From October 1973 through December 1975 a total of 118 serologically confirmed
pregnancy infections were detected in the area, 94 of which took place between
February and July 1974. The year following the outbreak showed scattered
cases, whereas the last half of 1975 was free of cases. The pairs of the
collection covered about one third of the pregnancy months occurring between
February 1974 through January 1975, and the rubella infections diagnosed by
seroconversion during this period indicated an attack rate for the epidemic
period of 2.8% pregnancy months, and 0.35% for the post-epidemic period.
50% of the infections went unrecognised
when they occurred, whereas only 17% seemed to have been subclinical.
It is estimated that at least 9 children may have been born with rubella
sequelae following infections during this period, when the legal abortions
because of rubella in taken into consideration.
Rubella in Jerusalem. 2. Clinical and serologic findings in
children with congenital rubella.
Isacsohn M, Nishmi M, Swartz TA.
Forty-eight children born with clinical and serologic manifestations of
congenital rubella were followed for a three-year period. Expanded rubella
syndrome, multiple anomalies and single defects were found, mostly in the
child's first year of life. Some new organic problems were found at a later
age in children who had initially been healthy but who had been followed up
because of their high antibody levels to rubella. Of the 48 children, 15 (31%)
were born to mothers who had had clinically and serologically diagnosed
rubella during pregnancy. In 33
children (69%) the mother had had asymptomatic rubella. These findings
emphasize the need to identify and immunize seronegative women before
pregnancy.
Rate and various aspects of eye infection resulting from
congenital rubella.
Romano A, Weinberg M, Bar-Izhak R, Mashiah S, Eylan E.
A study on the eyes of 39 embryos, which were removed from women who had
contracted clinical or subclinical rubella during the first and beginning of
the second trimester of gestation is presented. A virological and histological
study was performed on the eyes. In four cases rubella virus was isolated from
the eye tissues (10.3%) and in nine cases, histological evidence of rubella
cataract was found (27.3%). These
results suggest that the rubella infection, even in cases of subclinical
infections in pregnant women in the first trimester, are highly dangerous (in
our study--37.6%) to the eye of the fetus, and, therefore, early diagnosis is
necessary in order to avoid the risk of the consequences of congenital rubella
infections in the newborn.
Rubella vaccine. Recommendation of the Public Health
Service Advisory Committee on Immunization Practices. Center for Disease
Control, U.S. Department of Health, Education, and Welfare; Atlanta, Georgia.
Rubella infection may be subclinical
or overlooked because of the
nonspecificity of its most
frequent manifestations. Joint involvement is most frequent in women
but can occur in men and children. The most serious complication is induction
of fetal anomalies in infected pregnant women. This paper reviews the proper
use of live rubella virus vaccine for prophylactive immunization and the
postexposure treatment with immune serum globulin for modification or
suppression of symptoms.
Rubella epidemic in an institution: protective value of
live rubella vaccine and serological behavior of vaccinated, revaccinated and
naturally immune groups.
Baba K, Yabuuchi H, Okuni H, Harima R, Minekawa Y, Taniuchi M, Otsuka T,
Takahashi M, Okuno Y.
A rubella epidemic occurred in an institutional population composed of 189
susceptible, 37 naturally immune, 35 previously vaccinated and 38
serologically uncharacterized children and nursing staff. The epidemic lasted
3.5 months and showed more than 5 waves. Detailed clinical and serological
examinations of these subjects were made. A rash appeared in 156 (52%) of 299
persons, including 145 (87%) of 166 unvaccinated and serologically
uncharacterized subjects, but not in the 72 immune persons. In the middle of
the 3rd wave urgent vaccination of 61 children aged 0 to 2 years of the
susceptible group reduced the rate of appearance of a rash to 11 of the
children (18%), as compared with 126 (98%) of 128 subjects in the unvaccinated
non-immune group. The epidemic only reached a 4th wave in the vaccinated
group, but it extended to a 5th wave or more in unvaccinated subjects.
None of the 35 subjects in a
previously vaccinated group developed rubella, although the rate of
subclinical reinfection in this previously vaccinated group was higher (35%)
than that in the naturally immune group (17%). Three cases of subclinical
reinfection were detected even among 6 previously revaccinated subjects.
Serologic studies in 11,460
pregnant women during the 1972
rubella epidemic in Israel.
Fogel A, Gerichter CB, Rannon L, Bernholtz B, Handsher R.
A total of 11,460 women in the first 4 months of pregnancy, either exposed to
or with suspected clinical rubella were tested for rubella antibody during an
extensive epidemic of this disease in 1972. The proportion of women who were
seronegative decreased from 25% at the beginning of the epidemic to 16% toward
the end. In 542 (79%) of 682 cases with suspected clinical rubella, the
laboratory findings were consistent with recent rubella infection, while in
the remaining 140 cases of suspected clinical rubella recent infection could
be excluded by serologic tests. CF tests were more useful than HI for
confirmation of clinical rubella, and especially for retrospective diagnosis,
since elevated titers (larger than or equal to 1:16) were suggestive of recent
infection. Paired sera were tested from 4203 patients exposed to rubella: 1126
of the subjects were seronegative and the remaining 3077 seropositive (HI
larger than or equal to 1:16) on first testing. In the seronegative group, 278
seroconversions were detected (24.6%): 247 cases of clinical rubella (21.9%)
and 31 seroconversions without clinical symptoms (2.7%). Among the
seropositive subjects in 2306 instances (74.9%) recent subclinical rubella
could be excluded by low and stable HI or CF antibody titers in paired sera.
In 32 (1.1%) an antibody rise (HI or CF) without clinical symptoms was
detected, and in the remaining 739
(24%) high CF titers were found in paired sera, and these were classified as
suspected subclinical rubella.
Although rubella is the only virus which can be regarded in the strict sense
of the term a teratogen, there is no convincing evidence that other viruses
can cause fetal damage of varying severity. The risk to the fetus appears to
depend on the nature of the infectious agent, the maternal immune status and
the gestational age when infection takes place.
The possibility that subclinical
maternal infections may cause damage must not be overlooked. As some of
the viruses referred to can cause damage after the period of organogenesis,
the use of the term 'teratogenic efect' in relation to viral infections is
considered to be inappropriate.
ALL INFORMATION, DATA, AND
MATERIAL CONTAINED, PRESENTED, OR PROVIDED HERE IS FOR GENERAL INFORMATION
PURPOSES ONLY AND IS NOT TO BE CONSTRUED AS REFLECTING THE KNOWLEDGE OR OPINIONS
OF THE PUBLISHER, AND IS NOT TO BE CONSTRUED OR INTENDED AS PROVIDING MEDICAL OR
LEGAL ADVICE. THE DECISION WHETHER OR NOT TO VACCINATE IS AN IMPORTANT AND
COMPLEX ISSUE AND SHOULD BE MADE BY YOU, AND YOU ALONE, IN CONSULTATION WITH
YOUR HEALTH CARE PROVIDER.
