Age: 19.0
Sex: M
Vaccine: FLUN3, HEPAB, IPV, TD, YF, FLUN3, HEPAB, IPV, TD, YF, FLUN3, HEPAB, IPV, TD, YF
Symptoms: Culture negative, Culture throat negative, Disturbance in attention, Dyspnoea, Epstein-Barr virus antibody positive
Clinical narrative: This case was received from the Centers for Disease Control and Prevention (CDC), on 07 March 2008. A 19-year-old male received the following vaccines on 16 September 2007: MMR, polysaccharide pneumococcal vaccine, and meningococcal conjugate vaccine (manufacturers and lot numbers not provided). Prior to vaccination he had been in "excellent health", other than a brief episode the previous summer of sore throat and fever (up to 105 degrees), later attributed to viral illness. On 08 October 2007, he presented with sore throat, congestion, and purulent cough; a physical exam revealed swollen tonsils, and a chest x-ray was negative. Treatment included Cepacol, pseudoephedrine extended release, Tylenol, guaifenesin, oxymetazoline spray, and a Maalox/Lidocaine/Benadryl gargle. Symptoms improved over a few days. On 16 October 2007 he complained of a pruritic rash, which appeared primarily on his trunk and T-shirt area. He was diagnosed with urticaria, due to use of a new fabric softener, and treated with Benadryl. Later that day he received the following vaccines: YF-VAX (lot number UE912AA), IPOL (lot number Z0421), Diphtheria and Tetanus Toxoid (sanofi-pasteur, lot number as AC52B024AA), TWINRIX (GlaxoSmithKline, lot number AHABB100AA), and FLUMIST (MEDIMMUNE, lot number 500485P, inhaled). On 19 October 2007, three days after vaccination, he complained of watery nasal discharge, shortness of breath with exertion, temperature of 100.5 F, and headache. A repeat chest x-ray was negative, and he was treated with Tylenol, Cepacol, guaifenesin, pseudoephedrine LA, and Tessalon. On 26 October 2007, ten days after vaccination, the patient complained of headache and neck stiffness. He became lethargic and unresponsive, and "collapsed". He was taken to a clinic, where his temperature was noted to be 102.3 F. His Glasgow Coma scale rating went from a score of 14 (on a scale of 3 to 15) to 10, with incontinence. He underwent a lumbar puncture, and cerebrospinal fluid (CSF) WBC was found to be 2240 with 82% polys (polymorphonuclear leukocytes). He was treated with 1gm of Rocephin, 2 gm of ampicillin, acyclovir, and dexamethasone, and then evacuated by air to a nearby medical center with a presumed diagnosis of meningitis. He was admitted to the intensive care unit, where additional treatment included vancomycin and rifampin. A lumbar puncture reported on 27 October 2007 noted the CSF to be clear, with glucose 87 (normal 40-70), protein 66 (normal 12-60), WBC 75 (normal 0-8), RBC 98 (normal 0), "diff PMN 19%, L 28%, mono 53%". Gram stain was negative for organisms, initial meningococcal and S. pneumoniae antigen tests were negative, and cultures showed no growth after three days. PCR tests on CSF for herpes simplex viruses (HSVI and HSVZ), varicella-zoster virus, and HMV6 were also negative. Additional testing performed by the "Project" showed the following: Serum test WNV <0.5, IgM 0.03, Epstein Barr virus (IPA) >10, Epstein Barr Virus Nuclear Antigen >10, mycoplasma IGM negative, and Parvovirus B-19 IgM (IFA acute serum) <10. Chemistry profile revealed: sodium 132 (normal 136-144), potassium 3.3 (normal 3.6-5.1), chloride 98 (normal 101-111), BUN 5 (normal 8-26), Creatinine 0.6 (normal 0.7-1.2); serum cortisol was 1.50. Complete blood count showed: hemoglobin 13.8, hematocrit 40.6, and white blood count 9.4. Throat swab was negative for Influenza A and B, human metapneumovirus. RSV type A, enterovirus, and mycoplasma. A CT with contrast on 27 October 2007 showed only right sphenoid sinus disease, with no evidence of meningeal enhancement, intracranial hemorrhage, or parenchymal masses. An MRI on 29 October 2007 showed diffuse white matter increased signal without enhancement, a pattern "most suggestive to ADEM. This pattern could also be seen in the setting of Lyme disease". Serum lyme titer drawn 31 October 2007 was positive (45 kd IgG reactive), but Igm was negative (nonreactive).  The patient's mental status slowly improved, and after two days he was able to transfer out of the ICU. He remained hospitalized until 05 November 2007, at which time he was considered to be recovered to near baseline capacity. The discharge diagnosis was acute disseminated encephalomyelitis (ADEM). On 20 November 2007, the patient was seen by an infectious disease specialist disease as an outpatient. The consulting physician felt that ADEM was the probable diagnosis, in the setting of recent upper respiratory infection and recent vaccination and that the specific infectious etiology had not yet been identified. The patient was scheduled to ascertain yellow fever IgM levels; all testing was negative. Additional testing by the CDC detected no yellow-fever antibody post-vaccination, and no virus was isolated in the serum. RPR (rapid plasma regain) was also negative. On 21 November 2007 the patient had a follow-up appointment with a neurologist, at which time the patient stated that he was "back to about 75%" cognitively, with complaints of forgetfulness, difficulty concentrating, and slight weakness in the arms, legs, and hand grip. He also complained of decreased sensation in the fingers. Complete neurologic exam was normal, and he was referred for neurocognitive testing. This testing was performed on 28 November 2007, and revealed average to above-average results in all areas except verbal fluency, which was average. During an evaluation in the Vaccine Healthcare Center on 30 November 2007, the patient continued to complain of slight weakness and difficulty concentrating. A quality of life self-assessment, performed on 03 December 2007, revealed "slight decrements in perceived physical function, physical role, vitality,and physical component summary scales".  Nervous system disorder such as acute disseminated encephalomyelitis is listed event for yellow-fever vaccine. It needs to be underlined that the patient had experienced rhinorrhea, fever and shortness of breath 7 days before main symptoms of ADEM occurred. Nevertheless, etiology work-up for infectious etiologies is fairly exhaustive and the role of the yellow-fever vaccine needs to be considered.