Issue
Number 556
October 10, 2005
CONTENTS OF THIS ISSUE
- CDC reports on five cases of Guillain-Barre Syndrome
among recent recipients of Menactra meningococcal conjugate vaccine
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October 10, 2005
CDC REPORTS ON FIVE CASES OF GUILLAIN-BARRE SYNDROME AMONG RECENT RECIPIENTS
OF MENACTRA MENINGOCOCCAL CONJUGATE VACCINE
CDC published "Guillain-Barre Syndrome Among Recipients of Menactra
Meningococcal Conjugate Vaccine--United States, June-July 2005" in the
October 6 issue of "MMWR Dispatch." CDC publishes the web-based "MMWR
Dispatch" only for the immediate release of important public health
information. The article will be published in a print issue of MMWR in the
future.
The article is reprinted below in its entirety, with the exception of
acknowledgments and references. IMPORTANT: The article's Editorial Note
contains this important information for healthcare providers:
To date, evidence is insufficient to conclude that MCV4 [Menactra
quadrivalent meningococcal conjugate vaccine] causes GBS [Guillain-Barre
Syndrome]. An ongoing known risk for serious meningococcal disease exists.
Therefore, CDC is recommending continuation of current vaccination
strategies. Whether receipt of MCV4 vaccine might increase the risk for
recurrence of GBS is unknown; avoiding vaccinating persons who are not at
high risk for meningococcal disease and who are known to have experienced
GBS previously is prudent.
FDA and CDC are alerting healthcare providers to this preliminary
information and are actively investigating the situation because of its
potentially serious nature. The manufacturer has sent letters to healthcare
providers and is updating the package insert to reflect that GBS has been
reported in association with the vaccine. CDC recommends that adolescents
and their caregivers be informed of this ongoing investigation as part of
the consent process for vaccination with Menactra.
[IAC Express editor's note: Information about GBS has been added to an
interim Vaccine Information Statement (VIS) for meningococcal vaccine, dated
10/7/05. IAC Express will give readers additional information about the
interim VIS on 10/10/05.]
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On January 14, 2005, a quadrivalent (A, C, Y, and W135) meningococcal
conjugate vaccine (Meningococcal Polysaccharide Diphtheria Toxoid Conjugate
Vaccine, Menactra, sanofi-pasteur, Swiftwater, Pennsylvania) (MCV4) was
licensed in the United States. MCV4 is a tetravalent vaccine; each 0.5-mL
dose contains 4 [micrograms] each of capsular polysaccharide from Neisseria
meningitidis serogroups A, C, Y, and W-135 conjugated to 48 [micrograms] of
diphtheria toxoid. In February 2005, the Advisory Committee on Immunization
Practices (ACIP) recommended routine vaccination of adolescents at the
preadolescent healthcare visit (at ages 11-12 years). For persons who have
not been vaccinated previously, ACIP recommended vaccination before high
school entry (at approximately age 15 years). Routine vaccination also is
indicated for first-year college students living in dormitories and for
other persons at increased risk.
As of October 4, 2005, the Vaccine Adverse Event Reporting System (VAERS)
received five reports of Guillain-Barre syndrome (GBS) in persons after
receipt of MCV4 vaccination. VAERS, operated by CDC and the Food and Drug
Administration (FDA), is a national passive surveillance system that
monitors the safety of vaccines. Healthcare providers, state and local
health departments, consumers, and vaccine manufacturers are encouraged to
report adverse events involving all U.S.-licensed vaccines. All five persons
had been vaccinated during June 10-July 25. This report describes the
clinical and epidemiologic features of these five cases and summarizes
preliminary data from ongoing studies.
Case Reports
Case 1. A male aged 18 years was vaccinated with MCV4; 15 days later, he
experienced tingling in his feet and hands. He had no history of major
underlying illness; his mother had had GBS 5 years earlier. He reported no
history of respiratory or gastrointestinal illnesses during the 6 weeks
before onset of symptoms. Sixteen days after vaccination, he was
hospitalized, and nerve conduction studies (NCS) of upper and lower
extremities, 2 days after onset of symptoms, were consistent with GBS. He
was observed for 3 days, discharged, and then readmitted 2 days later with
bilateral facial weakness and increasing lower extremity weakness. Patellar,
triceps, and biceps deep tendon reflexes (DTRs) were absent. NCS performed 4
days after the previous examination revealed worsening motor nerve
conduction velocities consistent with GBS. Tests for mononucleosis and Lyme
disease were negative. During hospitalization, he was treated with
plasmapheresis. His facial palsy and gait improved, and his reflexes
returned. He was discharged home.
Case 2. A male aged 17 years was vaccinated with MCV4; approximately 25 days
later, he had difficulty walking, followed by difficulty moving from a
standing to a seated position. Medical history included attention deficit
hyperactivity disorder and Asperger syndrome; he had been taking multiple
psychotropic medications. He did not report recent respiratory or
gastrointestinal illness. Thirty-two days after vaccination, he was
hospitalized with bilateral muscle weakness of upper and lower extremities
with absent DTRs. NCS was consistent with GBS. Cerebrospinal fluid (CSF)
analysis revealed 2 white blood cells (WBC)/[cubic millimeter] with protein
of 60 mg/dL; bacterial cultures were negative. DNA polymerase chain reaction
(PCR) for adenovirus, herpes simplex virus types 1 and 2, varicella zoster
virus, cytomegalovirus (CMV), and Epstein-Barr virus (EBV), and RNA PCR for
West Nile virus, eastern equine encephalitis virus, St. Louis encephalitis
virus, enterovirus, and California group and Cache Valley viruses, were all
negative. During hospitalization, he was treated with intravenous
immunoglobulin (IVIG). On discharge, his motor strength and gait were
improved.
Case 3. A female aged 17 years was vaccinated with MCV4. She had a previous
history of GBS at ages 2 and 5 years, both beginning 14 days after
vaccination with childhood vaccines. She had not been previously vaccinated
with meningococcal vaccine. Both episodes of GBS were characterized by
muscle weakness, decreased reflexes, and difficulty walking. During both
episodes, she was treated with intravenous immunoglobulin and completely
recovered. Fourteen days after vaccination with MCV4, she reported numbness
of toes and tongue and had a lump in her throat. These symptoms were
followed by numbness of thighs and fingertips, arm weakness, inability to
run, difficulty walking, and falling. Sixteen days after vaccination, she
was hospitalized, and neurologic examination revealed decreased tone and
weakness of both arms and legs and reflexes reduced or absent in ankles,
knees, and arms. CSF results revealed 0 WBC/[cubic millimeter] and protein
26 mg/dL. She was treated with IVIG, recovered, and discharged home.
Case 4. A female aged 18 years was vaccinated with MCV4. Six days after
vaccination, she had a sore throat that lasted for 6 days, and 29 days after
vaccination she reported a severe headache and was evaluated in an emergency
department (ED), where she had a normal computerized tomography (CT) scan,
was treated with ketorolac, and discharged on oral ibuprofen. Thirty-one
days after vaccination, the patient reported numbness of legs and had
trouble standing on her toes. The next morning she could not stand. The
patient was admitted to the hospital, and physical examination revealed
decreased muscle strength in ankles and wrists bilaterally and reduced
biceps, knee, and ankle DTRs. Previous medical history included mild
ulcerative colitis that had been asymptomatic off medications; she did not
report having diarrhea during the 6 weeks before onset of muscle weakness.
Her only outpatient medications were oral contraceptives. CSF analysis
revealed 1 WBC/[cubic millimeter] and a protein concentration of 30 mg/dL.
NCS was consistent with GBS. She was treated with IVIG. After a 7-day
hospitalization, her motor strength had improved, and she was discharged
home with outpatient physical therapy. Three weeks after discharge, her
weakness and gait were improved.
Case 5. A female aged 18 years was vaccinated with MCV4; 14 days later, she
experienced heaviness in her legs when walking upstairs. During the next 8
days, her difficulty walking continued, and she had bilateral leg pain.
Subsequently, she reported headache, back and neck pain, vomiting, and
tingling in both hands. She became unable to walk and was evaluated in an
ED, where an initial diagnosis of viral meningitis was made. Two days later,
she was hospitalized for progressive weakness and inability to walk.
Neurologic examination revealed bilateral acute flaccid weakness with
decreased DTRs.
The woman had traveled to Portugal during the week before onset of symptoms
and had a history of seasonal allergies and sinusitis, but she reported no
history of respiratory, gastrointestinal, or other febrile illnesses during
the 3 months before onset. CSF examination revealed 5 WBC/[cubic millimeter]
and protein concentration of 177 mg/dL. Viral and bacterial cultures of CSF
were negative. EBV IgM, CMV IgM, ELISA serology for Lyme disease, and
serologic testing for syphilis were all negative. Electrodiagnostic studies
were consistent with GBS. Treatment included plasmapheresis and IVIG.
Weakness progressed to include paralysis of arms, difficulty swallowing, and
respiratory compromise. She required intubation for 1 week. She was
discharged to a rehabilitation facility, and 53 days after onset, she had
recovered the ability to talk, feed herself, sit, and stand.
Case Summary
All reported GBS cases occurred among persons aged 17-18 years who were
vaccinated during June 10-July 25 and had symptom onset 14-31 days after
MCV4 vaccination. On the basis of information obtained to date, one patient
reported another acute illness before onset of neurologic symptoms. The five
patients described in this report received vaccine from four different lots.
These cases were reported from Pennsylvania (two), New York, Ohio, and New
Jersey (one case each).
Editorial Note
GBS is a serious neurologic disorder involving inflammatory demyelination of
peripheral nerves. It can occur spontaneously or after certain antecedent
events such as infections. Illness is typically characterized by the
subacute onset of progressive, symmetrical weakness in the legs and arms,
with loss of reflexes. Sensory abnormalities, involvement of cranial nerves,
and paralysis of respiratory muscles also can occur. A small proportion of
patients die, and 20% of hospitalized patients can have prolonged
disability. Campylobacter jejuni, which causes bacterial gastroenteritis,
especially in young adults and during the summer months, is one identified
precipitating factor for GBS.
Approximately 2.5 million doses of MCV4 have been distributed nationally
since March 2005 (sanofi-pasteur, unpublished data, 2005). The number of
exact vaccine doses administered is unknown. The precise rate of GBS also is
unknown. Data from the Vaccine Safety Datalink (VSD), a collaborative
project between CDC and eight managed care organizations in the United
States, and the Health Care Utilization Project on GBS incidence in persons
aged 11-19 years indicate a background annual incidence of 1-2 cases per
100,000 person-years (CDC; Healthcare Utilization Project Nationwide
Inpatient Sample; Agency for Healthcare Research and Quality, unpublished
data, 1989-2001). This finding suggests that the rate of GBS based on the
number of cases reported within 6 weeks of administration of MCV4 is similar
to what might have been expected to occur by chance alone. However, the
timing of the onset of neurologic symptoms (i.e., within 2-5 weeks of
vaccination) is of concern. In addition, the extent of underreporting of GBS
to VAERS is unknown; therefore, additional cases might be unreported.
Prelicensure studies conducted by sanofi pasteur of approximately 7,000
recipients of MCV4 revealed no GBS cases. CDC has conducted a rapid survey
by using available VSD and other healthcare-organization databases. No cases
of GBS have been detected among nearly 110,000 MCV4 recipients represented
in these databases. Data from two VSD sites indicated that 86%-97% of
vaccine recipients had 6 weeks of follow-up via automated data collection.
These data do not rule out an association between MCV4 and GBS.
During 1999-2005, a total of 30 million doses
of three different meningococcal C conjugate vaccines (MenC), with either
diphtheria CRM (nontoxic variant of diphtheria toxin) or tetanus toxoid as
carrier proteins, have been used in the United Kingdom (UK) for persons aged
[younger than] 18 years. Five cases of GBS were reported in the UK after
administration of MenC vaccines (UK Department of Health, unpublished data,
2005). This reported number of cases is lower than would have been expected
to occur by chance in a population this age.
To date, evidence is insufficient to conclude that MCV4 causes GBS. An
ongoing known risk for serious meningococcal disease exists. Therefore, CDC
is recommending continuation of current vaccination strategies. Whether
receipt of MCV4 vaccine might increase the risk for recurrence of GBS is
unknown; avoiding vaccinating persons who are not at high risk for
meningococcal disease and who are known to have experienced GBS previously
is prudent.
FDA and CDC are alerting healthcare providers to this preliminary
information and are actively investigating the situation because of its
potentially serious nature. The manufacturer has sent letters to healthcare
providers and is updating the package insert to reflect that GBS has been
reported in association with the vaccine. CDC recommends that adolescents
and their caregivers be informed of this ongoing investigation as part of
the consent process for vaccination with Menactra.
FDA and CDC are requesting that providers or other persons with knowledge of
possible cases of GBS (or other clinically significant adverse events)
occurring after vaccination with MCV4 report them to VAERS. Reports of GBS
should be submitted to VAERS at
http://www.vaers.hhs.gov or by telephone at (800) 822-7967. CDC further
requests that healthcare providers report other cases of GBS that occur
among persons aged 11-19 years to state health departments in accordance
with state or local disease-reporting guidelines. CDC suggests that state
health departments consider enhancing surveillance for GBS in adolescents to
assist in answering these critical questions. Cases of meningococcal disease
should be reported to state health departments and, if available,
information on vaccination status should be provided; isolates should be
saved and sent to state health departments for serogroup identification.
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