Hlásenie nežiaducich účinkov na pandemickú vakcínu | Štátny ústav pre kontrolu liečiv

Zverejnené: 15.12.2009

Obsah

V čase vyhlásenia pandémie SZO sa očkuje veľké množstvo ľudí špeciálne pripravenými tzv. pandemickými vakcínami. Z toho dôvodu je potrebné, aby všetci všeobecní lekári pre dospelých, pre deti a dorast, ambulantní špecialisti a lekári na klinikách hlásili každé podozrenie na nežiaducu reakciu vakcíny, predovšetkým tie, patriace do týchto kategórií:

1. Závažné neočakávané nežiaduce reakcie

Neočakávaná reakcia je tá, ktorá nie je uvedená v súhrne charakteristických vlastností lieku

2. Smrteľné aleboživot ohrozujúce závažné nežiaduce reakcie

Vrátane každej hospitalizácie a predĺženia hospitalizácie v dôsledku nežiaducej reakcie

3. Nežiaduce reakcie zvláštneho významu (AESI):

a. Neuritída

b. Kŕče

c. Anafylaxia

d. Encefalitída, myelitída

e. Vaskulitída

f. Syndróm Guillain-Barré

g. Bellova obrna nervu facialis

h. Demyelizujúce ochorenie

i. Zlyhanie vakcinácie

Ich definície sú uvedené v prílohe.

Hlásenie sa zasiela na ŠÚKL a na najbližší Regionálny úrad verejného zdravotníctva Tlačivo hlásenia sú na (klikni sem): Tlačivo hlásenia

Pre správne zhodnotenie hlásenia je potrebné, aby boli uvedené aj tieto údaje:

a. Údaje opacientovi, vek, pohlavie, tehotenstvo, rizikové faktory
b. Kedy očkovaný, akou vakcínou, akou šaržou, akou dávkou, po ktorej dávke vporadí sa objavila reakcia.
c. Nežiaduci účinok, aké kritériá boli použité na diagnózu ochorenia, sú dostupné ďalšie údaje potrebné na diagnózu ochorenia?
d. Kto očkoval, špecialista, ktorý potvrdil diagnózu, kto hlásil

Pacientom, ktorí majú nežiaducu reakciu sa odporúča, aby navštívili svojho lekára a požiadali ho o vypísanie hlásenia nežiaduceho účinku. Bližšie údaje sú na (klikni sem): Rada pre pacientov - čo robiť v prípade vedľajšieho účinku?

Niektoré definície nežiaducich účinkov

Definície je možné nájsť na týchto adresách:

http://www.brightoncollaboration.org/intranet/en/index/document_download.html

http://www.cioms.ch/Vaccination_failure_Position_paper_final_080429.pdf

http://www.cioms.ch/publications/reporting_adverse_drug.pdf

Vaccination Failure

a) Confirmed Vaccination Failure

The occurrence of the specific vaccine-preventable disease in a person who is appropriately and fully vaccinated taking into account the incubation period and the normal delay for the protection to be acquired as a result of immunization.

This definition requires clinical and laboratory confirmation (or epidemiological link to a confirmed case) that the actual disease is vaccine preventable, i.e. that the pathogen (including, where appropriate, type, subtype, variant, etc.) and clinical manifestations are specifically targeted by the vaccine.

b) Suspected Vaccination Failure

Suspected vaccination failure is defined as the occurrence of disease in an appropriately and fully vaccinated person, but the disease is not confirmed to be the specific vaccine preventable disease, e.g. invasive pneumococcal disease of unknown serotype in a fully vaccinated person.

c) Immunological Failure

Immunological failure is defined as failure of the vaccinee to develop the accepted marker of protective immune response. This definition requires that there is an accepted correlate or marker for protection, and that the vaccinee has been tested/examined at an appropriate time interval after completion of immunization.

Adverse Events of Special Interest (AESI)

AESI Case definition Source

Neuritis. Optic neuritis: DeStefano et al. 2003

unilateral or bilateral visual loss, blurred vision, ophthalmic pain, and diagnosis of ON (confirmed by ophthalmologist) occurring within 6-week risk period after first vaccination

Vestibular neuritis: Baloh 2003

spontaneous, prolonged vertigo unilateral peripheral vestibulopathy, absence of other neurological symptoms or signs (confirmed by ENT specialist or neurologist) occurring within 6-week risk period after first vaccination

Convulsion Seizures: Bonhoeffer et al. 2004 Brighton Definition

Level 1 of diagnostic certainty:

Witnessed sudden loss of consciousness AND
Generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations

Level 2 of diagnostic certainty:

History of unconsciousness AND
Generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations

Level 3 of diagnostic certainty:

History of unconsciousness AND
Other generalized motor manifestations

Severe allergic reaction Anaphylaxis: Ruggeberg et al. 2007 Brighton Definition

For all levels of diagnostic certainty:

Anaphylaxis is a clinical syndrome characterized by

Sudden onset AND
Rapid progression of signs and symptoms AND
Involving multiple (>2) organ systems, as follows

Level 1 of diagnostic certainty:

>1 major dermatologic AND
>1 major cardiovascular AND/OR >1 major

respiratory criterion

Level 2 of diagnostic certainty:

>1 major cardiovascular AND >1 major

respiratory criterion OR

>1 major cardiovascular OR respiratory criterion

AND

>1 minor criterion involving >1 different system

(other than cardiovascular or respiratory system)

(>1 major dermatologic) AND (>1 minor

cardiovascular AND/OR minor respiratory

criterion)

Level 3 of diagnostic certainty:

>1 minor cardiovascular OR respiratory criterion

AND

>1 minor criterion from each of >2 different

systems/categories i

Major criteria

Dermatologic or mucosal

generalized urticaria (hives) or generalized

erythema

angioedema i i , localized or generalized
generalized pruritus, with skin rash

Cardiovascular

measured hypotension
clinical diagnosis of uncompensated shock, indicated by the combination of at least 3 of the

following:

o tachycardia

o capillary refill time >3s

o reduced central pulse volume

o decreased level of consciousness or loss of consciousness

Respiratory

bilateral wheeze (bronchospasm)
stridor
upper airway swelling (lip, tongue, throat, uvula, or larynx)
respiratory distress-2 or more of the following

o tachypnea

o increased use of accessory respiratory muscles (sternocleidomastoideus, intercostals, etc.)

o recession

The case definition should be applied when there is no clear alternative diagnosis for the reported event to account for the combination of symptoms not hereditary angioedema ii

o cyanosis

o grunting

Minor criteria

Dermatologic or mucosal

generalized pruritus without skin rash
generalized prickle sensation
localized injection site urticaria
red and itchy eyes

Cardiovascular

reduced peripheral circulation as indicated by the combination of at least 2 of the following:

o tachycardia and

o a capillary refill time of >3s without hypotension

o a decreased level of consciousness

Respiratory

persistent dry cough
hoarse voice
difficulty breathing without wheeze or stridor
sensation of throat closure
sneezing, rhinorrhea

Gastrointestinal

diarrhea
abdominal pain
nausea
vomiting

Laboratory

mast cell tryptase elevation > upper normal limit

Encephalitis Sejvar et al. 2007 Brighton Definition

Level 1 of diagnostic certainty: Encephalitis

1. Demonstration of acute inflammation of central nervous system parenchyma (+/- meninges) by histopathology

Level 2 of diagnostic certainty: Encephalitis

1. Encephalopathy (e.g. depressed or altered level of consciousness, lethargy, or personality change lasting > 24 hours)

AND including

2. ONE or MORE of the following

a. Decreased or absent response to environment, as defined by response to loud noise or painful stimuli

b. Decreased or absent eye contact

c. Inconsistent or absent response to external stimuli

d. Decreased arousability

e. Seizure associated with loss of consciousness

3. Focal or multifocal findings referable to the central nervous system, including one or more of the following

a. Focal cortical signs (including but not limited to: aphasia, alexia, agraphia, cortical blindness)

b. Cranial nerve abnormality/abnormalities

c. Visual field defect/defects

d. Presence of primitive reflexes (Babinski's sign, glabellar reflex, snout/sucking reflex)

e. Motor weakness (either diffuse or focal, more often focal)

f. Sensory abnormalities (either positive or negative, sensory level)

g. Altered deep tendon reflexes (hypo- or hyperreflexia, reflex asymmetry)

h. Cerebellar dysfunction, including ataxia, dysmetria, cerebellar nystagmus

AND (for both possibilities to reach level 2)

4. TWO OR MORE of the following indicators of inflammation of the CNS

a. Fever (temperature >38°C)

b. CSF pleocytosis (>5WBC/mm in children >2 months of age; >15 WBC/mm in children <2 months of age)

c. EEG findings consistent with encephalitis, or

d. Neuroimaging consistent with encephalitis

Level 3 of diagnostic certainty: Encephalitis

1. Encephalopathy (e.g. depressed or altered level of consciousness, lethargy, or personality change lasting >24 hours)

AND INCLUDING

2. ONE OR MORE of the following

a. Decreased or absent response to environment, as defined by response to loud noise or painful stimuli

b. Decreased or absent eye contact

c. Inconsistent or absent response to external stimuli

d. Decreased arousability, or

e. Seizure associated with loss of consciousness

3. Focal or multifocal findings referable to the central nervous system, including one or more of the following:

a. Focal cortical sign (including but not limited to: aphasia, alexia, agraphia, cortical blindness)

b. Cranial nerve abnormality/abnormalities

c. Visual field defect/defects

d. Presence of primitive reflexes (Babinski's sign, glabellar reflex, snout/sucking reflex)

e. Motor weakness (either diffuse or focal, more often focal)

f. Sensory abnormalities (either positive or negative, sensory level)

g. Altered deep tendon reflexes (hypo- or hyperreflexia, reflex asymmetry)

h. Cerebellar dysfunction, including ataxia, dysmetria, cerebellar nystagmus

AND (for both possibilities to reach Level 3)

4. ONE of the following indicators of inflammation of CNS

a. Fever (temperature >38°C)

3b. CSF pleocytosis (>5WBC/mm in children

>2 months of age; >15 WBC/mm³ in children <2 months of age)

c. EEG findings consistent with encephalitis, or

d. Neuroimaging consistent with encephalitis

Level 3A of diagnostic certainty

1. Insufficient information available to distinguish case between acute encephalitis or ADEM, case unable to be definitely classified

Exclusion criterion for level 2 and 3 diagnostic certainty

1. other diagnosis for illness present

Myelitis Sejvar et al. 2007 Brighton Definition

Level 1 of diagnostic certainty: Myelitis

1. Demonstration of acute spinal cord inflammation (+/- meninges) by histopathology

Level 2 of diagnostic certainty: Myelitis

1. Myelopathy (development of sensory, motor, or autonomic dysfunction attributable to the spinal cord, including upper- and/or lower-motor neuron weakness, sensory level, bowel and/or bladder dysfunction, erectile dysfunction).

AND

2. TWO OR MORE of the following indicators suggestive of spinal cord inflammation:

a. CSF pleocytosis (>5 WBC/mm³ in children >2 months of age; >15 WBC/mm³ in children <2 months of age)

b. Neuroimaging findings demonstrating acute inflammation (+/- meninges), or demyelination of the spinal cord

Level 3 of diagnostic certainty: Myelitis

AND

2. ONE of the following indicators suggestive of spinal cord inflammation

a. CSF pleocytosis (>5nWBC/mm³ in children >2 months of age; >15 WBC/mm³ in children <2 months of age)

b. Neuroimaging findings demonstrating acute inflammation (+/- meninges), or demyelination of the spinal cord

Exclusion criterion for Levels 2 and 3 of diagnostic certainty

1. other diagnosis for illness present

Cases fulfilling the criteria for both encephalitis and myelitis in any category would be classified as encephalomyelitis

Acute disseminated encephalomyelitis (ADEM) Sejvar et al. 2007 Brighton Definition

Level 1 of diagnostic certainty: ADEM

1. Demonstration of diffuse or multifocal areas of (ADEM) demyelination by histopathology

2. Focal or multifocal findings referable to the central nervous system, including one or more of the following:

a. Encephalopathy (see case definition for encephalitis for specification of encephalopathy)

b. Focal cortical signs (including but not limited to: aphasia, alexia, agraphia, cortical blindness)

c. Cranial nerve abnormality/abnormalities

d. Visual field defect/defects

e. Presence of primitive reflexes (Babinski's sign, glabellar reflex, snout/sucking reflex)

f. Motor weakness (either diffuse or focal, more often focal)

g. Sensory abnormalities (either positive or negative, sensory level)

h. Altered deep tendon reflexes (hypo- or hyperreflexia, reflex asymmetry)

i. Cerebellar dysfunction, including ataxia, dysmetria, cerebellar nystagmus

AND

3. Magnetic resonance imaging (MRI) findings displaying diffuse or multifocal white matter lesions on T2-weighted, diffusion-weighted (DWI), or fluid-attenuated inversion recovery (FLAIR) sequences (+/- gadolinium enhancement on T1 sequences)

AND

4. monophasic pattern to illness (i.e. absence of relapse within a minimum of 3 months of symptomatic nadir).

Level 2 of diagnostic certainty: ADEM

1. Focal or multifocal findings referable to the central nervous system, including one or more of the following:

a. Encephalopathy (see case definition for encephalitis for specification of encephalopathy)

b. Focal cortical signs (including but not limited to: aphasia, alexia, agraphia, cortical blindness)

c. Cranial nerve abnormality/abnormalities

d. Visual field defect/defects

e. Presence of primitive reflexes (Babinski's sign, glabellar reflex, snout/sucking reflex)

f. Motor weakness (either diffuse or focal, more often focal)

g. Sensory abnormalities (either positive or negative, sensory level)

h. Altered deep tendon reflexes (hypo- or hyperreflexia, reflex asymmetry)

i. Cerebellar dysfunction, including ataxia, dysmetria, cerebellar nystagmus

AND

2. Magnetic resonance imaging (MRI) findings displaying diffuse or multifocal white matter lesions on T2-weighted, diffusion-weighted (DWI), or fluid-attenuated inversion recovery (FLAIR) sequences (+/- gadolinium enhancement on T1 sequences)

AND

3. Insufficient follow-up time achieved to document absence of relapse within a minimum of 3 months of symptomatic nadir.

Level 3 of diagnostic certainty: ADEM

1. Focal or multifocal findings referable to the central nervous system, including one or more of the following:

a. Encephalopathy (see case definition for encephalitis for specification of encephalopathy)

b. Focal cortical signs (including but not limited to: aphasia, alexia, agraphia, cortical blindness)

c. Cranial nerve abnormality/abnormalities

d. Visual field defect/defects

e. Presence of primitive reflexes (Babinski's sign, glabellar reflex, snout/sucking reflex)

f. Motor weakness (either diffuse or focal, more often focal)

g. Sensory abnormalities (either positive or negative, sensory level)

h. Altered deep tendon reflexes (hypo- or hyperreflexia, reflex asymmetry)

i. Cerebellar dysfunction, including ataxia, dysmetria, cerebellar nystagmus

Level 3A

Insufficient information is available to distinguish case between acute encephalitis or ADEM; case unable to be definitively classified.

Exclusion criteria for all levels of diagnostic certainty

Presence of clear alternative acute infectious or other diagnosis for illness
Recurrent relapse of illness at any point following a 3 month period of clinical improvement from symptomatic nadir, or
If known, MRI findings or histopathology data inconsistent with the diagnosis of ADEM

Thrombocytopenia Wise et al. 2007 Brighton Definition

Level 1 of diagnostic certainty(confirmed TP)

Platelet count less than 150 x 10⁹/L

AND

Confirmed by blood smear examination OR the presence of clinical signs and symptoms of spontaneous bleeding

Level 2 of diagnostic certainty (unconfirmed TP)

Platelet count less than 150 x 10⁹/L

Level 3 of diagnostic certainty

Not applicable

Vasculitis Classification and Diagnostic criteria in systemic vasculitis Saleh and Stone 2005

Guillain-Barré syndrome According to Brighton definitions in preparation Brighton Definition in preparation

Bell's palsy Bell's palsy Gilden, 2004

Abrupt onset of unilateral facial weakness of peripheral cause in the absence of brain lesion and evidence for other causes of acquired peripheral facial weakness (diabetes, hypertension, HIV infection, Lyme disease, Ramsey Hunt syndrome, sarcoidosis, Sjögren syndrome, parotid nerve tumors, eclampsia, and amyloidosis) occurring within 6 weeks after first vaccination

REFERENCES

Baloh RW. Vestibular Neuritis. New Engl J Med 2003;348:1027-1032.

Bonhoeffer J, Menkes J, Gold MS, de Souza-Brito G, Fisher MC, Halsey N, and Vermeer P. Generalized convulsive seizure as an adverse event following immunization: case definition and guidelines for data collection, analysis, and presentation. Vaccine 2004;22: 557-562.

DeStefano F, Verstraeten T, Jackson LA, Okoro CA, Benson P, Black SB, Shinefield HR, Mullooly JP, Likolsky W, Chen RT. Vaccinations and Risk of central nervous system demyelinating disease in adults. Arch Neurol 2003;60:504-509.

Gilden, Donald H. Bell's Palsy. New Engl J Med 2004;351:1323-1331.

Ruggeberg JU, Gold MS, Bayas JM, Blum MD, Bonhoeffer J, Friedlander S, de Souza Brito G, Heininger U, Imoukhuede B, Khamesipour A, Erlewyn-Lajeunesse M, Martin S, Makela M, Nell P, Pool V, and Simpson N. Anaphylaxis: case definition and guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine 2007;25:5675-5684.

Saleh A, Stone JH. Classification and diagnostic criteria in systemic vasculitis. Best Practice & Research Clinical Rheumatology 2005;19:209-221.

Sejvar JJ, Kohl, KS, Bilynsky R, Blumberg D, Cvetkovich T, Galama J, Gidudu J, Katikaneni L, Khuri-Bulos N, Oleske J, Tapiainen T, and Wiznitzer, M. Encephalitis, myelitis, and acute disseminated encephalomyelitis (ADEM): case definitions and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine 2007;25: 5771-5792.

Wise RP, Bonhoeffer J, Beeler J, Donato H, Downie P, Matthews D, Pool V, Riise-Bergsaker M, Tapiainen T, and Varricchio F. Thrombocytopenia: case definition and guidelines for collection, analysis, and presentation of immunization safety data.

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