Table.

Clinical evaluation of selected AEFIs

Diagnosis/AEFI	Possible causes temporally related to AEFI other than immunization	Clinical evaluation to consider
Guillain-Barré syndrome14, 15, 39, 51	Viral: CMV,∗ EBV,∗ influenza A and B, varicella, HIV, HSV, adenovirus, parainfluenza, WNV	CSF, NP, serum, stool studies for listed viral and bacterial organisms of suspicion
	Other infectious causes: Campylobacter jejuni,∗Mycoplasma,∗Haemophilus influenzae, Borrelia	Consider saving pretreatment serum for acute and convalescent titer evaluation as IVIG or plasmapharesis is frequently used for treatment.
	Other: Surgery, head trauma
Transverse myelitis52, 53	Viral: Enterovirus (coxsackievirus A and B, poliovirus), hepatitis A and C, CMV, VZV, EBV, influenza, MMR	CSF, NPS, serum, stool studies for listed viral, bacterial, and parasitic organisms of suspicion
	Other infectious causes: Campylobacter, Mycoplasma, Brucella melitensis, Enterobius, Schistosoma	Evaluation for systemic autoimmune disorders
	Other diagnoses to consider: Systemic autoimmune disorders (MS exacerbation, SLE, systemic sclerosis, mixed connective tissue disorder)
ADEM31, 54, 55	Viral: MMR, VZV, EBV, CMV, HSV, hepatitis A and B, coxsackievirus, influenza A or B, HIV, HTLV-1, HHV6, vaccinia, human coronavirus	CSF, NPS, serum, stool studies for listed viral and bacterial organisms of suspicion
	Bacterial: Mycoplasma, Borrelia, Campylobactor, Leptospira, Chlamydia, Legionella, group A Streptococcus, Rickettsia	Consider saving pretreatment serum for acute and convalescent titer evaluation as IVIG or plasmapharesis is often used for treatment.
	Other: Paraneoplastic disorder, organ transplantation	Evaluation for systemic autoimmune disorders
	Other diagnoses to consider: Systemic autoimmune disorders
Encephalitis56	Viral: HSV, VZV, CMV, EBV, HHV6, La Crosse, Toscana, EEE, WEE, VEE, Chikungunya, JE, St. Louis, WNV, tick-borne encephalitis, Powassan/deer tick, Dengue, Reoviridae, Colorado tick fever, Picornaviridae, echovirus, coxsackievirus, poliovirus, enterovirus, HIV, Papovaviridae, JCV, BKv, influenza A and B, measles, mumps, Nipah, adenovirus, LCM, rabies, parvovirus B19	CSF, NPS, serum, stool studies for listed viral, bacterial, and parasitic organisms of suspicion.
	Other infectious causes: B. burgdorferi, B. henselae, Rickettsia/Ehrlichia/Anaplasma spp, M. pneumoniae, Toxoplasma gondii, Plasmodium spp, B. procyonis, Angiostrongylus/Gnathostoma spp, N. fowleri, Acanthamoeba spp, B. mandrillaris, Ameba, cysticercosis, fungi, meningitis, brain abscess, parameningeal abscess	Evaluation for acute and convalescent titers for infectious agents
	Other: Venous sinus thrombosis, autoimmune, Reye syndrome, ADEM, acute necrotizing encephalopathy, neoplasm, paraneoplastic disease, cerebrovascular, ischemic stroke, subdural/epidural hematoma, vasculitis, systemic conditions, metabolic conditions, connective tissue disorders, drug intoxication, epilepsy, head injury, confusion migraine	Evaluation for systemic autoimmune disorders, cerebrovascular disease, paraneoplastic disorder, or neoplasm
Aseptic meningitis57	Viral: Enteroviruses,∗ SLE, JE, WNV, Murry Valley, La Crosse, Jamestown Canyon, Snowshoe hare, HSV 1 and 2, VZV, EBV, CMV, HHV6, Colorado tick fever, mumps, LCM, measles, HIV, adenovirus, parainfluenza, influenza A and B, rotavirus, encephalomyocarditis, parvovirus B19	CSF, NPS, serum, stool studies for listed viral and bacterial agents
	Other: Toxins, C. pneumoniae	Serologic evaluation of acute and convalescent titers of infection
Afebrile seizure58, 59, 60, 61	Epilepsy, severe childhood epilepsies syndromes (Dravet, West, Doose, Lennox-Gastaut), cerebral dysgenesis	MRI (superior to CT unless need for urgent clinical management)
	Afebrile seizure associated with infection (rotavirus gastroenteritis)	EEG
	Neoplasm, trauma, nonaccidental trauma	Genetic analysis
		Rotavirus serology
Cerebellar ataxia61, 62, 63	Viral: VZV,∗ WNV, rubella, poliovirus type I, influenza A and B, mumps, EBV, parvovirus B19, hepatitis A, echovirus type 9, coxsackievirus type B	CSF analysis for listed agents
	Other infectious agents: Bacterial abscess, Mycoplasma, malaria, Legionella, meningococcal meningitis, typhoid	Serologic evaluation of acute and convalescent titers of suspected agents
	Other causes: Toxin (alcohol, insecticides, barbiturates, thallium, benzodiazepines, heavy metals, solvents), cerebrovascular (hemorrhage, thrombosis), multiple sclerosis, trauma, neoplasm, paraneoplastic syndrome, hereditary ataxia (Friedrich, ataxia telangiectasia, congenital cerebellar ataxia, Wilson disease, episodic ataxia, spinocerebellar ataxia, other inherited ataxias), cerebral palsy, heat stroke, metabolic disorders (mitochondrial, Hartnup disease, intermittent forms of maple syrup urine disease), hyponatremia, other autoimmune disorders (SLE)	Urine analysis for toxins
		MRI, CT
		Genetic analysis
		Evaluation for systemic autoimmune disorders
Optic neuritis64, 65, 66, 67	Viral: Measles, mumps, VZV, HHV6	CSF, NPS, serum studies for listed agents
	Other: Borrelia, Bartonella, Treponema pallidum	Serologic evaluation of acute and convalescent titers of infectious agents
	Other diagnoses to consider: Often the first presentation of multiple sclerosis, neuromyelitis optica, SLE, sarcoidosis, Sjögren syndrome	MRI for accurate diagnosis, extent of lesions
		Evaluation for systemic autoimmune disorders

BKv, BK virus; CMV, cytomegalovirus; CSF, cerebrospinal fluid; CT, computed tomography; EBV, Epstein-Barr virus; EEE, Eastern equine encephalitis; EEG, electroencephalography; HHV6, human herpes virus 6; HTLV-1, human lymphotropic virus-1; HSV, herpes simplex virus; IVIG, intravenous immunoglobulin; JCV, Jamestown Canyon virus; JE, Japanese encephalitis; LCM, lymphocytic choriomeningitis; MRI, magnetic resonance imaging; MS, multiple sclerosis; NPS, nasopharyngeal swab; SLE, systemic lupus erythematosus; VEE, Venezuelan equine encephalitis; VZV, varicella zoster virus, WEE, Western equine encephalitis; WNV, West Nile virus.

^∗Most commonly reported associations supported by biological evidence.