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FIGURE. Number of postvaccination syncope* episodes reported to the Vaccine Adverse Event Reporting System, by month and year of report - United States, January 1, 2004-July 31, 2007

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* Includes persons aged >5 years who had syncope onset after vaccination on the same date.

Meningococcal conjugate vaccine. $ Date on which the Advisory Committee on Immunization Practices decided to add this newly licensed adolescent vaccine to the Vaccines for Children

Program. 1 Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine. Quadrivalent human papillomavirus recombinant vaccine. HPV is licensed only for females.

doses distributed in 2004, 0.31 per million doses distributed in 2005, and 0.54 per million doses distributed in 2006. Compared with reports received during 2002–2004, those received during 2005–2007 were more likely to involve females (61.1% versus 77.5%) or persons aged 11-18 years (47.3% versus 62.0%) (Table). In 292 (63.1%) of the 463 reports during 2005–2007, syncope was associated with at least one of the following recently approved and recommended adolescent vaccines: MCV4, Tdap, and HPV.

Thirty-three (7.1%) of the 463 postvaccination syncope reports during 2005–2007 were coded as serious (Table); the percentage was not substantially different from the corresponding 20 (9.9%) serious reports during the earlier comparison period. After clinical review, seven of the reports coded as serious were excluded because they were either not compatible with the diagnosis of syncope (n = 4) or did not meet the criteria of seriousness (n = 3); 26 reports of serious adverse events were analyzed further.

The 26 patients ranged in age from 11 to 84 years (median 18 years), and 20 (76.9%) were female. Similar to the fine ings for syncope reports overall, females aged 11-18 vear accounted for the largest number of serious syncopa reports (n = 11 [42.3%]). Among the 23 patients for whor times of vaccination and syncope onset were indicated, 12 (52.2%) occurred within 5 minutes of vaccination, and 16 (69.6%) occurred within 15 minutes. Ten of the 26 serous reports indicated that secondary injuries occurred afte syncope, including head injuries (n = 9) after syncoperelated falls and a motor-vehicle incident (n = 1) because the patient lost consciousness while driving. Seven (70.00 of the 10 secondary injuries occurred within 15 minutes of vaccination. Reported by: A Sutherland, MD, H Izurieta, MD, R Ball

, MD MM Braun, MD, Div of Epidemiology, Center for Biologics Evaluaines and Research, Food and Drug Admin. ER Miller, MPH, KR Broder, MD BA Slade, MD, JK Iskander, MD, Immunization Safety Office, Office in the Chief Science Officer; AT Kroger, MD, Immunization Sves Div, Natas Center for Immunization and Respiratory Diseases; LE Markowitz, MD Div of STD Prevention, National Center for HIV/AIDS, Viral Heparin STD, and TB Prevention; WT Huang, MD, EIS Officer, CDC

2007 data not yet

available.

BOX. Recommendations and guidance on preventing postvaccination syncope and secondary injuries

SABLE. Number and percentage of postvaccination syncope

pisodes reported to the Vaccine Adverse Event Reporting (stem, by selected characteristics — United States, January 2002-July 31, 2007 2002-2004

2005-2007 (N = 203)

(N = 463) haracteristic No. (%)

No. (%)

X emale

124 (61.1)

359

(77.5) Tale

79 (38.9)

96 (20.7) Inknown

0 (0.0)

8 (1.8) je group (yrs) 5-10

24 (11.8)

32 (6.9) 1-18

967
(47.3)

2878

(62.0) 9-49

59 (29.1)

114

(24.6) 0-64

13 (6.4)

12 (2.6) >65

11 (5.4)

18 (3.9) verity erious

(9.9)

33 (7.1) Ionserious

183 (90.1)

430 (92.9) acluding persons aged 25 years who had syncope onset interval after accination on the same date. l'emales: 49 (24.1%); males: 47 (23.1%). emales: 229 (50.3%); males: 58 (12.7%).

Vaccine providers should strongly consider observing patients for 15 minutes after they are vaccinated. If syncope develops, patients should be observed until

symptoms resolve. • Personnel should be aware of presyncopal manifesta

tions and take appropriate measures to prevent injuries if weakness, dizziness, or loss of consciousness occurs. The relative rapid onset of syncope after vaccination in most persons suggests that having vaccine recipients sit or lie down for 15 minutes after vaccination could prevent many syncopal episodes and secondary injuries. If syncope develops, patients should be observed until symptoms resolve.

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* CDC. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices. MMWR 55(No. RR-15); 2006. † American Academy of Pediatrics. Active immunization. In: Pickering LK, ed. 2006 red book: report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006.

ditorial Note: During 2005–2007, ACIP decided to add veral newly licensed adolescent vaccines to the routine imunization schedule and the Vaccines for Children Proam. After these vaccines were licensed and recommended r use, the number of postvaccination syncope reports to AERS increased, primarily among females aged 11-18 ars. Although only 7% of the reports met the criteria for eing classified as serious, potentially life-threatening juries after postvaccination syncope were described, and ne fatality was documented, resulting from intracranial morrhage caused by head trauma in a boy aged 15 years 1. ACIP and the American Academy of Pediatrics have iblished recommendations to prevent postvaccination synpe and related injuries (Box) (4,8). These preventive straties apply to all ages and all types of vaccines. However, e observed increase in postvaccination syncope and secidary injuries suggests that adherence to the 15-minute ostvaccination observation period and its efficacy in prenting syncope-related injuries should be evaluated sysmatically The findings in this report are subject to at least four nitations. First, because of underreporting and lack of e-specific data on vaccine doses administered, the rates lculated from VAERS data do not represent the actual cidence rates of postvaccination syncope. The rates might

underestimated in this report because the denominars used in the analysis were calculated from vaccine doses stributed, not doses administered, and syncope reports ere excluded for children aged <5 years, the population

that receives the majority of vaccine doses. Second, hypotheses generated from VAERS need additional clinical and epidemiologic analysis (5). Although this report indicates that vaccines most commonly noted in VAERS syncope reports are universally recommended for adolescents, this age group also has a higher background rate of syncope than other age groups (9). The predominance of female patients in syncope reports could reflect an actual difference in the occurrence of syncope between the sexes (9). However, this predominance also could be a result of reporting bias; the currently licensed HPV was recommended in a 3-dose series for females only, and MCV4 and Tdap were each recommended for single-dose use in both sexes. Third, MedDRA coding terms might not accurately reflect the diagnosis of syncope. The number of postvaccination syncope reports might be either underestimated because certain syncope episodes might also be categorized as seizures or convulsions (2) or overestimated because certain near-syncope or nonsyncope reports might be misclassified as syncope. Finally, clinical details of nonserious reports were not reviewed; for example, although current recommendations suggest a 15-minute postvaccination observation period, data regarding distribution of minutes of time lapsed from vaccination to syncope were not reviewed for nonserious reports.

All providers administering vaccinations should be aware of the potential for syncope after vaccination and should take appropriate measures to prevent potential injuries. If syncope develops, patients should be observed until symptoms resolve. In accordance with ACIP recommendations, providers should strongly consider observing patients for 15 minutes after they are vaccinated (4). References 1. Ost LG, Sterner U, Lindahl IL. Physiologic responses in blood phobics.

Behav Res Ther 1984;22:109-17. 2. Braun MM, Patriarca PA, Ellenberg SS. Syncope after immunization.

Arch Pediatr Adolesc Med 1997;151:255-9. 3. Newman BH, Graves S. A study of 178 consecutive vasovagal syncopal

reactions from the perspective of safety. Transfusion 2001;41:1475-9. 4. CDC. General recommendations on immunization: recommendations

of the Advisory Committee on Immunization Practices (ACIP). MMWR

2006;55(No. RR-15). 5. Varricchio F, Iskander J, DeStefano F, et al. Understanding vaccine

safety information from the Vaccine Adverse Event Reporting System.

Pediatr Infect Dis J 2004;23:287–94. 6. Rosenthal S, Chen R. The reporting sensitivities of two passive surveil

lance systems for vaccine adverse events. Am J Public Health

1995;85:1706–9. 7. Woo EJ, Ball R, Braun MM. Fatal syncope-related fall after immuniza

tion. Arch Pediatr Adolesc Med 2005;159:1083. 8. American Academy of Pediatrics. Active immunization. In: Pickering

LK, ed. 2006 red book: report of the committee on infectious diseases.

27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006. 9. Driscoll DJ, Jacobsen SJ, Porter CJ, Wollan PC. Syncope in children

and adolescents. J Am Coll Cardiol 1997;29:1039–45.

Case Report

On September 19, 2007, a man aged 46 years visited as outpatient facility with paresthesia in his right hand. Dus ing the next 3 days, the paresthesia spread proximally, ani the patient developed flaccid weakness in the right uppe: extremity. Electromyography (EMG) performed at a loca outpatient facility on September 24 revealed evidence o axonal nerve damage. Within 3 days, the patient devel. oped paresthesia and weakness in his left upper extremir and gait unsteadiness. Magnetic resonance imaging (MRI of the brain on September 28 was unremarkable, but MR of the cervical spine showed central spinal cord T2-signa abnormalities with associated edema spanning the C3 C6 levels, suggestive of an inflammatory process.

On September 29, the patient had a fever of 101.107 (38.4°C) and was hospitalized. He developed double visios tremulousness, and rapidly progressive respiratory failure which required intubation and ventilator support the neu: morning. He had no laryngospasm or dysphagia. Analix of cerebrospinal fluid (CSF) by lumbar puncture reveale a pleocytosis of 12 cells/mm3 (normal: 0–5 cells/mm 85% lymphocytes, elevated protein of 107 mg/dL (norma 15–45 mg/dL), normal glucose, and negative bacterial cu ture and acid-fast bacilli screening. West Nile virus and herpes simplex virus testing of the CSF were negative bi polymerase chain reaction (PCR). Additional CSF studio were negative for cryptococcal antigen, antibody for syphilis and Lyme disease antibody. The patient's serum was negative for evidence of antinuclear antibodies, extractable nucler antibodies, or antibody to West Nile virus, Borrelia sp Treponema pallidum, Mycoplasma pneumoniae, humar. T-lymphotropic virus I and II, human immunodeficiency virus and hepatitis A, B, and C viruses. Because his clinical and labe ratory profiles were suggestive of idiopathic transverse mer tis, he was treated with intravenous methylprednisolone.

The patient's symptoms did not improve, and his feve: reached 102.7°F (39.3°C). In three procedures, MRIO the brain did not demonstrate significant abnormalities but MRI of the spinal cord revealed progressive extension of the previously detected cervical segment abnormalities He became comatose on October 5 and had no clinica evidence of cranial nerve function except infrequent spen taneous respiration. A repeat lumbar puncture showed normal white blood cell count of 1 cell/mm', elevated protein of 75 mg/dL, normal glucose, and eight unique oligoclonal bands by electrophoresis (normal: none indicative of immunoglobulin production by plasma cell and central nervous system disease. The CSF immunoglo-! bulin G synthesis rate by spectrophotometry was border

Human Rabies Minnesota, 2007

On October 20, 2007, a Minnesota resident died from rabies, approximately 1 month after initial symptoms of limb paresthesia, which progressed to flaccid weakness and ataxia. This was the only human rabies case reported in the United States in 2007. A presumptive diagnosis of idiopathic transverse myelitis was considered initially, because of abnormalities detected via spinal cord imaging studies and a lack of laboratory confirmation of a specific infectious etiology. The presumptive diagnosis subsequently was changed to include rabies, based on the patient's rapidly deteriorating neurologic status and elicitation of a history involving bat exposure during the month before illness onset. This report summarizes the medical and epidemiologic investigation by the Minnesota Department of Public Health and CDC and the ensuing public health response. The findings underscore the need for early inclusion of rabies in the differential diagnosis of rapidly progressive encephalitis, improved public awareness of the risks associated with animal bites, and appropriate rabies prophylaxis after exposure.

biopsy samples by reverse transcription-PCR; therefore, antigenic characterization and genetic sequencing of the rabies virus variant were not possible. Because of the poor prognosis, medical care was withdrawn after extended family discussions, and the patient died on October 20, the twenty-second day of hospitalization.

ne elevated at 12.04 (normal: <12), consistent with an -ngoing inflammatory process. Bacterial cultures of CSF

'mained negative, and additional CSF evaluation showed egative viral PCR tests for cytomegalovirus, Epstein-Barr rus, enterovirus, and herpes simplex virus. Analysis of CSF so was negative for neuromyelitis optica antibody, associ

ed with Devic's disease. Repeat neuroimaging on Octo-er 7 revealed further caudal to rostral progression of the -- rainstem and spinal cord abnormalities observed on

'ctober 5. Because of progressive neurologic decline, the atient was transferred to a tertiary-care center.

On arrival at the tertiary-care center, the patient was matose with a Glasgow coma score of 3 without demonrable cranial nerve function. A neurologic examination 'vealed flaccid quadriparesis and hyporeflexia. EMG

vealed severe, acute polyradiculoneuropathy. Auditory oked potential testing indicated absent responses. With le presumptive diagnosis of idiopathic transverse myeliį, the patient was treated with methylprednisolone and asmapheresis. On October 15, CSF analysis revealed a cocytosis of 22 cells/mm3 (94% lymphocytes), red blood :ll count of 2,519 cells/mm3 (normal: 0 cells/mm2), evated protein of 235 mg/dL, normal glucose, and irther elevated immunoglobulin G synthesis rate of 3 mg/24 hours (normal: -9.9 to 3.3 mg/24 hours). MRI

the brain revealed new symmetric T2-signal abnormalies within the basal ganglia and medial temporal lobes, ith subtle leptomeningeal gadolinium enhancement. he ascending paralysis and coma appeared atypical of iopathic transverse myelitis, and the patient's clinical proession and brain imaging abnormalities were noted to semble those observed in rabies encephalitis (1). Once rabies was suspected, the patient's family was terviewed on October 16 for a history of potential expore. According to his family, the patient had handled a

it with his bare hands in a semi-open cabin porch in north* ntral Minnesota on August 19, 2007. He had reported *eling a needle prick sensation before releasing the bat.

ecause no blood or wound was visible, the patient conuded he had not been bitten and did not seek medical

tention. Neither the patient nor his family was aware that Is is exposure constituted a rabies risk.

On October 17, specimens of the patient's serum, CSF,

liva, and a nuchal biopsy were sent to CDC. Rabies virus Etibodies were detected in stored CSF and serum samples

llected before plasma exchange, confirming the suspected agnosis. However, no rabies virus antigens were detected

the skin biopsy using fluorescent microscopy, and no bies virus amplicons were detected in saliva or skin

Public Health Investigation

After diagnosis of rabies, the Minnesota Department of Health assessed the need for rabies postexposure prophylaxis (PEP) among close contacts of the patient and healthcare workers and searched the likely site of rabies exposure. Family members, other close contacts, and health-care workers were interviewed using a standard questionnaire to identify possible exposures to the patient's saliva. Three of 14 family contacts and 51 of 524 health-care workers who participated in the man's care received rabies PEP, administered chiefly at the respective hospital emergency departments. The Minnesota Department of Health received no information from health-care providers suggesting incomplete PEP administration or adverse events resulting from rabies vaccination. Although a search of the cabin site on October 26 revealed no evidence of bat infestation, given the reported bat exposure on August 19, initial symptoms on September 19, and an incubation period of approximately 1 month, investigators concluded that a bite from a bat was the most likely source of rabies virus infection. Reported by: AH Yee, DO, RT Merrell, MD, AY Zubkov, MD, PhD, AJ Aksamit, MD, WT Hu, MD, PhD, EM Manno, MD, Mayo Clinic, Rochester; J Scheftel

, DVM, A De Vries, MD, D Neitzel, MS, R Danila, PhD, KE Smith, DVM, PhD, Minnesota Dept of Health. CE Rupprecht, VMD, PhD, Div of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases; S Holzbauer, DVM, EIS Officer, CDC. Editorial Note: This report describes the only reported case of human rabies in the United States in 2007 and the first case in Minnesota since 2000. Investigators determined that the likely source of rabies in this case was a bat. In Minnesota, bats and skunks are the only known reservoirs of rabies. In 2006, 42 rabid animals were reported in the state, including 17 bats and 20 skunks (2).

During 2000–2007, a total of 25 cases of human rabies were reported in the United States (2). Eighteen (28%) cases were associated with suspected exposure to rabid bats or infection with bat rabies virus variants. Most of these human cases occurred in late summer or early autumn, coincident with a seasonal increase in the prevalence of rabid bats detected in the United States (2). Despite repeated documentation of human rabies attributable to bat exposures and identification of 1,212–1,692 rabid bats

up

References 1. Hu WT, Willoughby RE Jr, Dhonau H, Mack KJ. Long-term follow

after treatment of rabies by induction of coma. N Engl J Na 2007;357:945-6. 2. Blanton JD, Hanlon CA, Rupprecht CE. Rabies surveillance in ou

United States during 2006. J Am Vet Med Assoc 2007;231:540_56. 3. Liesener AL, Smith KE, Davis RD, et al. Circumstances of bat encos

ters and knowledge of rabies among Minnesota residents submitting

bats for rabies testing. Vector Borne Zoonotic Dis 2006;6:213–20. 4. CDC. Human rabies prevention—United States, 1999: recommer.cz

tions of the Advisory Committee on Immunization Practices. MHUX

1999;48(No. RR-1). 5. Willoughby RE Jr, Tieves KS, Hoffman GM, et al. Survival after

treatment of rabies with induction of coma. N Engl J Med. 2014 352:2508-14.

more

in the United States during 2000–2006, the significance of bat exposures often is ignored (3,4).

The animal contact, incubation period, clinical presentation, and laboratory findings for the patient described in this report were typical of human rabies cases reported in the United States. However, a diagnosis of rabies was not considered until the clinical course appeared atypical of the presumptive diagnosis of idiopathic transverse myelitis and brain imaging abnormalities resembled those observed in rabies. One unusual facet of this case was the inability to detect viral antigens or nucleic acids in patient samples, although rabies virus antibodies were identified in the serum and CSF. The only other human rabies case in the United States in which viral antigens or nucleic acids could not be detected, since such laboratory methods became m widely available in the early 1990s, was a 2004 Wisconsin patient, who survived rabies after a bat bite (1,5). However, the Wisconsin patient was an adolescent girl treated successfully with a drug-induced coma and antiviral drugs, and the significance of any similarities between that case and the Minnesota case is unclear.

This report underscores the need for increased public awareness of the risks of direct contact with bats and other wild animals. After exposure, human rabies is preventable with timely and appropriate PEP, consisting of proper wound care and prompt administration of rabies biologicals (4). Rabies PEP is recommended for all persons with direct transdermal or mucous membrane exposure to a bat, unless the animal is found not to have rabies. However, bite lesions from certain animals, including bats, can be difficult to detect. Consequently, proper tailoring of health communications to medical practitioners and the public remains a challenge to ensure that appropriate PEP is administered when indicated but not unnecessarily.

Rabies should be considered in the differential diagnosis of human cases involving acute, rapidly progressive encephalitis, especially when the clinical course and neuroimaging findings are compatible, regardless of history of animal exposure (1,4). If a patient is unresponsive, interview of family members and close contacts might reveal potential exposures. Prompt diagnosis of rabies can enable rapid case investigation, implementation of appropriate infection-control measures, and consideration of experimental therapy (5).

Report from the Advisory
Committee on Immunization

Practices (ACIP): Decision Not to Recommend Routine Vaccination

of All Children Aged 2-10 Years with Quadrivalent Meningococcal

Conjugate Vaccine (MCV4) At its February 2008 meeting, the Advisory Committee on Immunization Practices (ACIP) decided not to recormend routine vaccination of children aged 2-10 year against meningococcal disease unless the child is at increased risk for the disease. This report summarizes the delibera tions of ACIP and the rationale for its decision and restais existing recommendations for meningococcal vaccination. among children aged 2-10 years at increased risk for meningococcal disease. ACIP continues to recommend routira vaccination against meningococcal disease for all person: aged 11-18 years and those persons aged 2–55 years

wa are at increased risk for meningococcal disease (1-3).

On October 17, 2007, the Food and Drug Administra tion added approval for use of quadrivalent meningococca conjugate vaccine (MCV4) (Menactra®, Sanofi Pasteur Swiftwater, Pennsylvania) in children aged 2-10 years ! existing approval for use in persons aged 11-55 years (7 Before licensure of MCV4, quadrivalent meningococca polysaccharide vaccine (MPSV4) (Menomune®, Sanof Pasteur) was the only meningococcal vaccine available in the United States. MPSV4 was recommended for routine use only among persons at increased risk for meningococcal disease (1). Because clinical efficacy trials were not feasible in the United States, MCV4 licensure was based on clinical trials in which the safety and immunogenicity of MCV4 was compared with MPSV4. Immunogenicity was measured by serum bactericidal activity (SBA), a correlate

Acknowledgments The findings in this report are based, in part, on contributions by M Junna, MD, A Frye, MD, Mayo Clinic, Rochester, Minnesota; and R Franka, DVM, PhD, M Niezgoda, MS, L Orciari, MS, and P Yager, Div of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases, CDC.

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