Fever
Dr. F.Deniz Aygün
Istanbul University-Cerrahpasa
Cerrahpaşa Faculty of Medicine, Department of Pediatrics, Division of
Pediatric Infectious Diseases, Istanbul
Etymology
• Latin→ febris (heat)
• Greek→pyrexia ‘pyr’: fire
• Severe and fatal illness causes continuous fever
• One of four signs of inflammation
What is fever?
Pyrexia, febrile response
Increased body heat more than normal
• Fever: The increase of body temperature by
thermoregulator pyrogens via hypothalamus (generally
due to infections or inflammatory conditions)
• 10-20% of the applications to the outpatient clinic are
fever and inflammatory diseases
• About 4-6 episodes of fever per year can be seen in
children in the first two years of life
Definition
• The mean normal temperature is generally considered to be 37°C
• In newborns, normal body temperature is considered to be 37.5-38 ° C
• Young children and babies have higher body temperature due to their high
basal metabolic rate and the high ratio between body surface area and
weight
Definition
• Normally body temperature shows a diurnal change during the day
• Lowest in the early morning and highest between 16:00 and 18:00
• There may be 0.5 ° C difference between morning and evening
• This rhythm usually continues during the febrile period
• Exercise, excessive dressing, hot bath, extremely hot weather, hot food and drinks
can raise the body temperature up to 38-38.5 ° C in a healthy child
Definition
• The best indicator of body temperature is core body temperature
• The central body temperature is determined by measurement from
the pulmonary artery
• Generally, a body temperature of ≥ 38 ° C (rectal) in children is
considered to be fever
Definition
• Can be measured from oral, rectal, axillary, tympanic membrane and forehead skin
• The normal ranges of fever vary according to the area of measurement
• Rectal fever is the closest to body core temperature and should be considered as a
reference
• Rectal measurement is contraindicated in a neutropenic patient
• Orally measured temperature is 0.6 ° C lower than rectal temperature
• Oral temperature is affected by conditions such as oral cold or hot food and tachypnea
Definition
• Axillary measurement is the most commonly preferred
• Measurement from tympanic membrane is close to core
• Contact or non-contact infrared forehead thermometers measure the heat
generated by the temporal artery
• They are affected by vascular changes and sweating status, so they are not
recommended to be used in making decisions about the patient's clinical
condition
Site and method of measurement
• ≤ 1 MONTH : Electronical axillary
• 1 month-5 years: Electronical axillary
Infrared tympanic
Rectal
Which values exceed the body temperature ıs
considered as fever
• Axillary > 37.4°C
• Oral > 37.5°C
• Rectal > 38°C
• Tympanic > 37.8°C
Hyperthermia
• Increased body heat without the contribution of pyrogens
• Generally caused by excessive heat exposure or by failed thermoregulation
• Not considered a fever
• Behavioral changes such as chills and shaking are generally not expected
• The simplest statement to distinguish fever and hyperthermia; The person
with a fever feels cold and the hyperthermic person feels his body warming
Hyperthermia
• Cyclooxygenase inhibitors have no place and benefit in treatment
• Treatment is mainly to eliminate the cause
• It is based on correction of fire with cold application
Pathophysiology
POA: preoptic area
PGE2:prostaglandin E2
LPS: lipopolysaccharide
OVLT: organum
vasculosum lamina
terminalis
In the classic model of fever pathogenesis, exogenous
pyrogens stimulate the release of circulating endogenous
pyrogens, which act via prostaglandins to increase the set
point of the hypothalamic thermoregulatory center
FEVER
Infections
Toxins
Injuries
Heat production and
conservation
Inflammation
Immunologic responses
Increase threshold to febrile levels
Monocytes
Lymphocytes
Neutrophils
Endothelial glial cells
Hypothalamic Thermoregulatory Center
Mesenchymal cells
Prostaglandine E2
Pyrogenic cytokines
IL-1, IL-6, TNF, INF
Blood circulation
Pyrogens
• Exogenous pyrogens
• Microorganisms
• Endogenous pyrogens
• IL-1, IL-6, TNF alpha
Is fever beneficial or harmful?
• Although there has been a lot of clinical debate that fever is
beneficial, it is not conclusively scientifically proven
• Fever is a symptom, not a disease
• Fever is a defense response that the body develops against harmful
factors
• A certain level of fire works to the benefit of the organism
Is fever beneficial or harmful?
• Inhibits the growth of microorganisms
• Increases the anti-microbial activity
• Antibiotics are more efficient
• Increases antibody production and T lymphocyte proliferation
• Inflammation system works better
When to treat fever?
• There is no suggestion that when a fever occurs in a previously
healthy child, it should be reduced immediately
• There is no evidence of a reduction in mortality and morbidity when
fever is reduced
• However, in some chronic diseases, high fever may cause an increase
in metabolic rate and worsening of the underlying disease
When to treat fever?
Above 39-40 º C
If there is a susceptibility for seizures
Pregnant women
Seniors
Individuals with heart issues
Individuals with pulmonary, renal or cerebral disease
Causes
• Infections
• Connective tissue disorders
• Cancers
• Hypersensitivity reactions
• Drugs
Fever types
Continuous fever
Intermittent fever
Remittent fever
Undulant fever
Recurrent fever
Continuous fever
•
•
•
•
•
The variation between maximum and minimum temperature in 24 hours is less than 1 °C
Temperature doesn’t touch the baseline
Pneumonias, thyphoid fever, meningitis
Typhoid fever; step ladder fever, high plateau
If accompanied by relative bradycardia: thyphoid fever, leischmaniasis, brucellosis
Thyphoid fever
Intermittent fever
• Temperature is elevated for several hours followed by an interval
when temperature drop backs to normal
• This type of fever usually occurs during the course of an infectious
disease
Intermittent fever in malaria
• Plasmodium
falciparum
• Plasmodium
vivax/ovale
• Plasmodium
malariae
• Every 24 hours
• Quotidian fever
• Every 48 hours
Tertian fever
• Every 72 hours
Quartan fever
Remittent fever
• Fever with daily fluctuations exceeding 2 °C but at no time touches
normal
Remittent fever
• Mostly infectious causes
• Infective endocarditis, ricketsiosis, brucella…
Undulent fever
• The fever is rising and falling like a wave (remittent fever pattern),
accompanied by weakness, headache, chills and weight loss
• Caused by brucellosis
Pel Ebstein fever
• A rarely seen condition in
Hodgkin’s lymphoma
• Fevers which cyclically increase
then decrease over an average
period of one two weeks
Fever of unknown origin (FUO)
• Prolonged febrile illness without an established etiology
despite thorough evaluation
• Temperature >38.3°C for at least three weeks
• And undiagnosed after one week of medical evaluation
• The causes include infections, connective tissue disorders,
cancers …..
Fever of unknown origin (FUO)
• In children, the term fever of unknown origin should be reserved for
fever of at least 8 days’ duration and for which no diagnosis is
apparent after the initial workup in the hospital or as an outpatient
BOX
63.1
Causes of Fever of Unknown Origin in Children
Infectious Diseases
Bacterial
Bacterial endocarditis
Brucellosis
Cat-scratch disease
Leptospirosis
Liver abscess
Mastoiditis (chronic)
Osteomyelitis
Pelvic abscess
Perinephric abscess
Pyelonephritis
Salmonellosis
Sinusitis
Subdiaphragmatic abscess
Tuberculosis
Tularemia
Viral
Adenovirus
Arboviruses
Cytomegalovirus
Epstein-Barr virus (infectious mononucleosis)
Hepatitis viruses
Chlamydial
Lymphogranuloma venereum
Psittacosis
Rickettsial
Q fever
Rocky Mountain spotted fever
Fungal
Blastomycosis (nonpulmonary)
Histoplasmosis (disseminated)
Parasitic
Malaria
Toxoplasmosis
Visceral larva migrans
Unclassified
Sarcoidosis
Collagen Vascular Diseases
Juvenile rheumatoid arthritis
Polyarteritis nodosa
Systemic lupus erythematosus
Malignancies
Hodgkin disease
Leukemia and lymphoma
Neuroblastoma
Miscellaneous
Central diabetes insipidus
Drug fever
Ectodermal dysplasia
Factitious fever
Familial dysautonomia
Granulomatous colitis
Hemophagocytic lymphohistiocytosis
Infantile cortical hyperostosis
Kikuchi-Fujimoto disease
Nephrogenic diabetes insipidus
Pancreatitis
Periodic fever
Serum sickness
Thyrotoxicosis
Ulcerative colitis
Fever without source
• Fever without source is the occurrence of fever for 1 week or less in a
child in whom a careful history and physical examination fail to reveal
a probable cause of the fever
• One concern regarding a young child with FWS is the possibility that
the child has occult bacteremia
• The risk for occult bacteremia developing in a child with FWS is age
related, with the greatest risk occurring in the first few months of life
Summary
• Fever is an abnormal increase in body temperature that results from
elevation of the hypothalamic set-point
• Fever is an important clinical sign
• The first step in the management of fever is to determine its cause
• The cause of fever should be evaluated, particularly in infants
younger than three months of age and infants and children with
underlying medical conditions that increase the risk of serious
infection
• Once the cause is known, the main reason to treat fever is to improve
the child's comfort
Childhood Febrile Illness with
Skin Rashes
Dr. F.Deniz Aygün
Pediatric Infectious Diseases
What is a rash?
• A rash is defined as a widespread eruption of skin lesions
• Exanthem is any eruptive skin rash
• Enanthem is a rash on the mucous membranes
Rashes?
• Macules are nonpalpable lesions <1 in diameter, develop due to capillary
dilatation, the redness fades with pressing
Scarlet fever
Rashes?
• Papules are palpable lesions <1 cm in diameter, develop due to
extravascular serum, the redness fades with pressing
Rashes?
• Purpura is red-purple lesions that do not blanch under pressure,
resulting from the extravasation of blood from cutaneous vessels into
the skin
• Purpuric lesions can be macular or raised (palpable purpura)
• Petechia is the smaller form
Rashes?
• Vesicles are small (<1 cm in diameter), circumscribed skin papules
containing clear serous or hemorrhagic fluid
• Bullae are large (>1 cm in diameter) vesicles
• Pustules are small, circumscribed skin papules containing purulent
material
vesicle
bullous
Rashes?
• Erythema is redness of the skin or mucous membranes, caused by
hyperemia (increased blood flow) in superficial capillaries
Rashes?
• Nodular
• Similar to papule
• Located deeper in the dermis or subcutaneous
Erythema
nodosum
Why important?
• Lethal?
• Requires isolation?
• Anti-microbial therapy?
How to distinguish?
history
Physical
exam
Laboratory
data
Diseases Presenting with Fever and Rash
DISEASE
Rubeola
ETIOLOGY
Measles virus
DESCRIPTION OF RASH
Macular-papular rash that
may become confluent;
begins on face, neck and
shoulders and spreads
centrifugally and inferiorly;
fades in 4 to 6 days
EPIDEMIOLOGY
Most common in
children 5 to 9
years of age,
nonimmune
persons
DIAGNOSTIC CLUES
Prodrome consisting of symptoms of upper
respiratory tract infection, coryza, bark-like
cough, malaise, photophobia and fever,
Koplik's spots (prodromal stage);
development of exanthem on fourth febrile
day; late winter through early spring
a
rors
Serology
Measles
• Maculopapular
• Rash appears when respiratory complaints are most intense
• Approximately two to four days after onset of fever
• 14 days after exposure
Measles
• Stimson line characterized by transverse line of inflammation along
the eyelid margin
• The severity of conjunctivitis is variable and may also be accompanied
by lacrimation or photophobia
• Enanthem characterized by 1 to 3 mm whitish, elevations with an
erythematous base, typically seen on the buccal mucosa opposite the
molar teeth
Diseases Presenting with Fever and Rash
DISEASE
Rubella
ETIOLOGY
Rubella virus
DESCRIPTION OF RASH
EPIDEMIOLOGY
Pink macules and papules
that develop on forehead
and spread inferiorly and to
extremities within one day;
fading of macules and
papules in reverse order by
third day
=
Young adults,
nonimmune
persons
Tuna
Measles vs. Rubella
DIAGNOSTIC CLUES
Prodrome uncommon, especially in children;
petechiae on soft palate (Forschheimers
spots); in adults: anorexia, malaise,
conjunctivitis, headache and symptoms of
mild upper respiratory infection
BASIS
FOR
DIAGNOSIS
Serology
Rubella
• Minimal systemic symptoms
• Pinpoint, pink
• One by one, do not come together
• Low grade fever
• Catarrhal findings are milder than measles in the prodromal period
• Cough not obvious
• No photophobia
Rubella
The lymphadenopathy characteristically involves the posterior cervical, posterior auricular, and suboccipital lymph nodes
(Thedor Sign)
An enanthem on the soft palate (Forchheimer spots)
Diseases Presenting with Fever and Rash
DISEASE
Erythema
infectiosum (fifth
disease)
ETIOLOGY
Human
parvovirus B19
DESCRIPTION OF RASH
Begins as classic bright-
red facial rash (“slapped
cheek) and progresses to
lacy reticular rash; may
wax and wane for 6 to 8
weeks
EPIDEMIOLOGY
Children 3 to 12
years of age
DIAGNOSTIC CLUES
PANO
Can present as rheumatic syndrome in
Serology
adults; prodrome of fever, anorexia, rash
Erythema infectiosum
The classic erythematous malar rash appears with relative circumoral pallor
(the so-called slapped cheek rash)
This facial rash is often followed several days later by a reticulated or lacelike
rash on the trunk and extremities
Diseases Presenting with Fever and Rash
DISEASE
ETIOLOGY
DESCRIPTION OF RASH
Roseola
Human herpesvirus 6
Diffuse maculopapular
eruption, usually sparing
face
EPIDEMIOLOGY
Children 6 months
to 3 years of age
DIAGNOSTIC CLUES
Fever lasting 3 to 4 days, followed within 2 to
3 days by the rash, which resolves
spontaneously in several days; almost
always a self-limited benign disease;
temporal relationship of fever followed by
rash is helpful in making the diagnosis
BASIS FOR
DIAGNOSIS
Clinical
findings,
serology
Roseola Infantum/exanthem subitum, sixth
disease
• High fever (may exceed 40°C ) that resolves abruptly and followed by
development of a rash
• The fever often is accompanied by irritability, although most children
with roseola are otherwise well-appearing, active, and alert
Petechial eruptions
• Petechial rashes warrant immediate evaluation to rule out severe life
threatening illness!!
meningococcemia
Meningococcemia
• Infants, asplenic patients, complement deficiencies
• Midwinter months
• N.meningitis A,C,Y,W,B
• It is bacterial septicemia characterized by fever, tachycardia,
hypotension, and meningitis
• Shock and diffuse intravascular coagulation disorder are the main
pathogenesis
IN CASE OF FEVER WITH PETECHIA IT IS MENINGOCOCSEMIA UNTIL
PROVEN OTHERWISE
Meningococcemia
• Petechiae can coalesce into larger purpuric and ecchymotic lesions
• The petechiae correlate with the degree of thrombocytopenia and
clinically are important as an indicator of the potential for bleeding
complications secondary to disseminated intravascular coagulopathy
Petechial eruptions
• Rocky mountain spotted fever
• Rickettsia rickettsii
• Tick bite
Vesiculobullous-pustuler eruptions
Varicella zoster virus (VZV)
Varicella (chickenpox)
• Primary infection with
VZV
Herpes zoster (shingles)
• Reactivation of VZV
Varicella
• The lesions begin as macules that rapidly become papules followed by
characteristic vesicles
• Maculopapule → papule → vesicle → pustule → crust
• The patient with varicella typically has lesions in different stages of
development on the face, trunk and extremities
Hand-foot and mouth disease
• Oral enanthem and a macular, maculopapular, or vesicular rash of the
hands and feet (and possibly other locations)
• Most commonly on the tongue and buccal mucosa
• Vesicles quickly rupture and form superficial ulcers with a yellow base
and an erythematous rim
Hand-foot and mouth disease
• The exanthem typically involves the hands (dorsum of the fingers,
interdigital area, palms)
• Feet (dorsum of the toes, lateral border of the feet, soles, heels), buttocks,
legs (upper thighs)
Diffuse erythema with desquamation
• Scarlet fever
• 1-10 years of age
• Group A beta hemolytic streptococci
• Diffuse erythema that blanches with pressure, with numerous small (1 to 2 mm)
papular elevations, giving a "sandpaper" quality to the
• Followed by desquamation
Scarlet fever
Linear petechial character in the
antecubital fossae and axillary folds,
known as Pastia's lines
Scarlet fever
Circumoral pallor and a strawberry tongue
Scarlet fever
White strawberry tongue in first two days (Hyperkerotic membran)
At the 4-5.days red strawberry tongue (membrane lifts, shiny mucosa)
Pharynx and tonsillar hyperemic edema and exudate
Petechiae can be seen on the soft palate
Diffuse erythema with desquamation
Toxic Shock Syndrome and Scalded Skin Syndrome
• Staphylococcus aureus
• Hypotension, erythema, fever, multisystem dysfunction
Kawasaki disease
Kawasaki Disease
CRASH and BURN mnemonic:
BURN =5 days of fever AND 4 out of 5
C—conjunctivitis (usually bulbar, bilateral, non-purulent)
R—rash (just about anything except vesicles, bullae)
A-— adenopathy (usually cervical, singular, >1.5cm)
S$ — strawberry tongue (or other changes like lip redness, cracking)
H — hand and feet swelling/erythema, (peeling later in course)
AHA guidelines:
http://circ.ahajourn
als.org/content/13
5/17/e927.long
Or < 6 months old and unexplained fever > 7 days regardless of above criteria
¥
Order CRP, ESR, CBC, albumin, ALT, UA with micro
Admit for IVIG and Echo
supplementary lab criteria:
Albumin < 3
Anemia for age
ALT elevated (> 50)
Platelets > 450,000 after 7 days of fever
WBC > 15
Urine WBC > 10/hpf
Arithritis
Subacute
Convalescent
bo
Cardiovascular | Myocarditis
Skin
—
YES
Acute
Fever
Incomplete Kawasaki: suspect if 5+ days of fever and 2-3 of above criteria
CRP>3 or ESR> 40 AND 3 or more
Clinical manifestations of Kawasaki Disease
5
ore
E
a.
Lips &
Conjunctiva
Cervical
:
Lymphadenopathy
Echo
ES
CRP >3 or
ESR > 40?
Follow daily until
fever resolves
echo
get g,
NO | If peelin
Seaton K, Kharbanda A. Evidence-Based Management of Kawasaki Disease in the Emergency Department. Pediatric Emergency Medicine
Practice. 2015 12(1); 1-24.
:
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Thrombocytosis
Weeks
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Erythema nodosum
Erythema nodosum
• A delayed-type hypersensitivity reaction that most often presents as
erythematous, tender nodules on the shins
• Infection is the most commonly identified etiology, with streptococcal
infection the most common cause
Erythema nodosum
Approach to patient with fever and rash
history
Prof.Dr.Emel Gür
Immunization
 Immunization is one of the most benefical and costeffective disease prevention measures
 Immunization is the process of inducing immunity
against a specific disease
 Smallpox has been eradicated
 Polio is close to world-wide eradication
Active Immunization
 Active immunity develops as a result of infection or by active
immunization
 Active immunization is protection by vaccination ( administration
whole or part of a microorganism or a modified product of a
microorganism)
 Result in protective humoral and celluler responses in the recipient
 Immunity and immunologic memory similar to natural infection but
without risk of disease
 Some immunizing agents provide nearly complete protection againts
disease
 Some provide partial protection and requre readministered at regular
intervals to maintain protection
Vaccine preventable diseases
• Tuberculosis
•
Typhoid Fever
• Yellow fewer
•
Rabies
• Japanese encephitis
•
Tick-borne enephalitis
• Cholera
•
Malaria
• Smallpox (eradicated in 1980)
Routine Childhood Vaccines
 BCG
 TDaP
 Td
 Hib
 IPV
 OPV
 HepB
 HepA
 MMR
 VAR
 PCV
(Bacillus-Calmette-Guerin vaccine)
(diphtheria-tetanus- acelluler pertussis vaccine)
(adult type tetanus-diphtheria vaccine)
(H. influenzae type b vaccine)
(Inactivated polio vaccine)
(oral polio vaccine)
(hepatitis B vaccine)
(hepatitis A vaccine)
(measles-mumps-rubella vaccine)
(varicella vaccine)
(pneumococcal conjugate vaccine)
Non-Routine Childhood Vaccines
 RV1 (monovalent human rotavirus vaccine; G1P8)
 RV5 (pentavalent human-bovine reassortant rotavirus vaccine; G1,G2,G3,G4 and G9)
 MCV4 (meningococcal conjugate vaccine serogroups Men ACYW135)
 MPSV4 (meningococcal polysaccharide vaccine serogroups Men ACYW135
 MenB (seroroup B meningococcal vaccine)
 Men A, C, A/C (meningococcal polysaccharide vaccines seroroups (A; C and A/C )
 MenC (meningococcal conjuge vaccine seroroup C)
 PPSV23 (23 valent pneumococcal polysaccharide vaccine)
 IIV (inactivated İnfluenza vaccine; influenza A (H1N1), influenza A (H2N3), influenza B viruses)
 LAIV (live attenuated influenza vaccines ; influenza A (H1N1), influenza A (H2N3), influenza B
 9vHPV (nonavalent human papillomavirus vaccine)
 4vHPV (quadrivalent human papillomavirus vaccine)
 2vHPV (bivalent human papillomavirus vaccine)
 Tdap (adult type tetanus-diphtheria-acelluler pertussis vac.)
Content of Vaccine
 Active immunizing agents/antigens
 Adjuvants
 Conjugating agents
 Suspending fluid
 Preservatives/stabilizers/antimicrobial agent
Active Immunizing Agents
 Live attenuated virus; MMR, VAR, OPV, RV, LAIV,
yellow fewer vaccine
 Inactivated virus; IPV, Hep A, Rabies, Japanese
encephalitis
 Inactivated viral components ;IIV (viral surface
glycoprotein), HepB, HPV (viral proteins by
recombinant technology)
 Live Bacteria; BCG, typhoid vaccine (ty21a)
 Inactivated bacterial components; DTaP, Hib, PPSV,
PCV, MPSV, MCV
Other Immunizing Agents
 Adjuvants; For increasing immunogenicity and prolonging the
stimulatory effect in inactivated vaccines
*Aluminum salt (Aluminum hydroxide )(DTaP, DT, Td, HepB, HepA)
*ASO4 (monophosphory lipid A) (HPV2)
 Preservatives/stabilizers/antimicrobial agents; antibiotics, chemicals (eg.
trace amounts of thimerosal (ethyl mercury- only some inactivated
influenza vaccine) .For preventing bacterial contamination and antigen
degregation
 Suspending fluid; sterile water, saline solutions, complex tissue-culture
(eg. egg antigens, gelatin)
 Conjugating agents; carrier proteins (tetanus toxoid-T, nontoxic diphteria
toxin-D, meningococcal outher membrane protein complex-OMP)
bound to polysaccharide antigens for enhancing immune responsesin
children younger than 2 years of age (eg. Hib, PCV, MCV)
Classification of vaccines
Live attenuated
 Bacterial :Bacillus Calmette Guerin (BCG), typhoid(Ty21a)
 Viral :Oral polio (OPV), Mumps-Measles-Rubella(MMR),Varicella
(VAR), İnfluenza (LAIV), rotavirus (RV), yellow fewer vaccines
Inactivated
 Whole: Inactivated polio virus (IPV), rabies, hepatitis A (HepA), Japanese
ensephalitis vaccines
Fractional:
*Protein based :
-Toxoid(DT,Td),
- Subunit inactivated influenza vaccine (IIV)
- Hepatit B vaccine (HepB),
- Human papilloma virus vaccine (HPV)
*Polysaccharide-based (pure, conjugate)
-Pure; Pneumococcal polysaccharide vaccine (PPV-23),
Meningococcal polysaccharides vaccine (MPSV4)
-Conjugate; Pneumococcal conjugate vaccine (PCV-13), Meningococcal
conjugate vaccine (MCV4), Haemophilus influenzae type b (Hib)
Vaccine Storage and Handling
 Vaccines should be stored and transported at recommended
temperatures
 All vaccines licensed for refrigerator storage should be stored
at 2-8 °C (35-46°F)
 Live viruse vaccines are heat sensitive (MMR, VAR, rotavirus,
OPV, LAIV, yellow fever vaccines)
 Inactivated vaccines are cold sensitive
(DTaP, DT,Td,Tdap, IPV, Hib, PPSV, PCV, MPSV, MCV, HepB, HepA, IIV)
• Some vaccines must be protected from light by keeping in its
original carton (MMR, BCG,VAR,IIV,RV, MCV, HPV, Hib )
Cold Chain Menagement
Cold chain management includes all of the means used to ensure a constant
temperature (between +2°C and +8°C) for a product that is not heat stable (such as
vaccines, serums, tests, etc.), from the time it is manufactured until the time it is
Vacine Storage
Freezer
Ice packs
Stock tracking
Top shelf
OPV,MMR,VAR,Measles
No vaccine
indoors
Middle shelf
BCG,DTaP-IPV-Hib,
Rabies, antiserum
Bottom shelf PCV,
HepB,HepA, DT, Td,
TT, diluents
Fridge Tag
Heat Tracking
Water bottles
All vaccines licensed for refrigerator
storagshould be stored at 2-8 °C
Health care professionals follow appropriate procedures for vaccine storage and handling
Equipment for Vaccine Transport
Insulated Container
ii
CI
=
without insulating materials
2
i
fi
Time limits for using vaccines after reconstitution
*MMRs 8
hrs
*BCG < 4-8 hrs
*Varicella < 30 min
protect from ligth
General Instructions of Vaccine Administration
 Because of a severe allergic reaction to a vaccine





component, people administering vaccines should be
prepared to recognize and treat allergic reactions (eg
anaphylaxis)
Hand hygiene should be used before and after each new
patient contact
Syringes and needle must be sterile and disposable
Changing needles between drawing a vaccine into a syringe
and injection it into achild is not necessary
Different vaccines should no be mixed in the same syringe
unless specifically licensed and labeled for such use
Observe people 15-30 minutes after they are immunized
for anaphylaxis
Site and Route of Immunization
 Oral Vaccines: (OPV ,RV)

*Breastfeeding does not interfere with successfull immunization
*Vomiting within 10 minutes ; repeating dose of OPV, but not RV
İntramuscular injections:DTaP, DT,Td, Hib, IPV ,HepB, HepA,PCV,MCV
*Needle should be administered 90° angle,
*22-25 gauge needle (according to age)
*For the children <1 yr of age ; anterolateral aspect of thigh
*For the older children; deltoid area of upper arm
*Apply firm pressure at the immunization site for at least 2 minute
 Subcutaneous injections: MMR,VAR, PPSV, MPSV,
*Needle should be administered 45° angle,
* Insert the needle pinched up of fold of skin
* Anterolateral aspect of the thigh or upper outer triceps area
* 23-25 gauge needle
 Intracutaneous injections: BCG
*Needle should be administered 15° angle
*25-27 gauge needle
*Insert the needle into epidermis by stretching of skin
 Intranasal: LAIV
Routine Vaccines
Types
Routes of
Administration
BCG
Live-attenuated bacteria
İntracutaneous
(Bacillus-Calmette-Guarin)
(DT aP-IPV/Hib (PRP-T)
Diphtheria-acellular pertussis- tetanusinactive poliovirus /Haemophilus
influenzae type B
DTaP-IPV
Toksoids and inactivated bacterial
Intramuscular
components-inactivated
virus/bacterial polysaccharide-protein
conjugate
Toksoids and inactivated bacterial
components-inactivated virus
Intramuscular
Toxoids
Intramuscular
Hep B (Hepatitis B)
Recombinant viral antigen
Intramuscular
Hep A (Hepatitis A)
Inactivated virus
Intramuscular
MMR (measles-mumps-rubella)
Live –attenuated virus
Subcutaneous
VAR (Varicella)
Live –attenuated virus
Subcutaneous
OPV (oral poliovirus)
Live- attenueted virus
Oral
Diphtheria-acellular pertussis- tetanus-
inactive poliovirus
DT, Td
Diphtheria-tetanus, adult type
diphtheria-tetanus
PCV13 (Pneumococcal conjugate) Bacterial polysaccharide-protein conjugate
Intramuscular
Routine Immunization Schedule-Turkey
BIRTH
Hep B
BCG
DaPTIPV-Hib
PCV
I
1.
MO
2
MOS
4
MOS
II
6
MOS
12
MOS
18
MOS
24
MOS
I
I
II
I
II
III
R
R
I
R
I
VAR
R
DaPTIPV
I
II
R
Td
Hep A
11-12
YRS
III
MMR
OPV
4-6
YRS
I
II
Bacillus-Calmette-Guarin)
BCG Vaccine
Live-attenuated bacterial vaccine for tuberculosis disease
(expectially, childhood tuberculous meningitis and miliary disease)
BCG is used in many countries with a high prevalence of TB
•Routine vaccination:
• Administer only one dose at the end of the 2months (0,05 mL <1 yr, 0.1 mL >1 yr, ic)
•Catch-up vaccination:
•BCG vaccination should only be considered for children who have a negative
tuberculin skin test (PPD reaction <5mm) for children older then 3 months of age
•The tuberculosis skin test is also known as the tuberculin test or PPD purified
protein derivative test
•The standard recommended tuberculin test is the Mantoux test, which is
administered by injecting a 0.1 mL volume containing 5 TU (tuberculin units) PPD
into the top layers of skin of the forearm
•Skin tests should be read 48-72 hours after the injection
Hepatitis B (HepB) vaccine
Recombinant viral antigen for Hepatitis B infection
Minimum Age: At birth
Routine vaccination:
• Administer monovalent HepB vaccine to all newborns before hospital discharge.
• The second dose should be administered at age 1 or 2 months
•The final dose in the HepB vaccine series should be administered at age 24 weeks (no
earlier than age 24 weeks)
•Hep B vaccination should be deferred in infants weighing<2 kg at birth until 30 days of
age ( for child of HBsAg (-) mother) and they should receive an additional 3 doses of
vaccine starting at 30 days of age
Administration: 0,5 mL im
Catch-up vaccination:
• Unvaccinated persons should complete a 3-dose series
•The minimum interval between dose 1 and dose 2 is 4 weeks and between dose 2 and 3
is 8 weeks. The final (third or fourth) dose in the HepB vaccine series should be
administered at least 16 weeks after the first dose.
Diphtheria and tetanus toxoids and acellular pertussis
(DTaP) vaccine
DTaP-Purified tetanus toxoid- purified diphteria toxoid- acellular pertussis
(pertussis toxin, filamentous hemagglutinin, pertactin, fimbriae v.s)
Minimum age: 6 weeks
Routine vaccination: Administration: 0,5 mL im
• Administer a 5-dose series of DTaP vaccine at ages 2, 4, 6, 18 months, and at
ages 4 through 6 years , adult type tetanus-diphtheria toxoids (Td) vaccine at ages
11-12 years, than repeat every ten years
•The fourth dose may be administered as early as age 12 months, provided at
least 6 months have elapsed since the third dose.
Catch-up vaccination:
•The minimum interval is 4 weeks between dose 1 and dose 2 and between dose
2 and dose 3
•The minimum interval is 6 months between dose 3 and dose4, and between
dose 4 and dose 5
• The fifth (booster) dose of DTaP vaccine is not necessary if the fourth dose was
administered at age 4 years or older.
Infections caused by Hib
Haemophilus influenzae type b (Hib)
conjugate vaccine
•Meningitis
•Pneumonia
•Epiglottitis
Bacterial polysaccharide-protein conjugate vaccine for Hib
PRP-T -Purified Polyribosyl Ribitol Phosphate (capsular polysaccharide isolated
from Hib) – tetanus toxoid protein
Minimum age: 6 weeks
Routine vaccination: Administration: 0,5 ml im
• The primary series doses should be administered at 2, 4, and 6 months
of age (PRP-T)
•One booster dose should be administered at age 18 months
Catch-up vaccination-Hib
Administration Time
Minimum Interval Between Doses
First dose
dose 1-dose 2
dose 2-dose 3
dose 3-dose 4
<6 mo
4 wks
4 wks
8 wks
7-11 mo
4 wks
8 wks
12-15 mo
8 wks
15 ay-59 mo
only one dose vaccination (no further doses needed)
Infections caused by
S.pneumoniae
– Sepsis
– Meningitis
– Pneumonia
Pneumococcal conjugate vaccine (PCV).
– Sinusitis
– Otitis media
Bacterial polysaccharide-protein conjugate vaccine
– Conjunctivitis
13 v PCV (PCV13) Streptococcus pneumoniae serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14,
18C, 19A, 19F,23F -protein carrier CRM197
Minimum age: 6 weeks
Routine vaccination: Administration: 0,5 mL im
• Administer a series of PCV13 vaccine at ages 2, 4 months with a booster at age 12
months
Catch-up Vaccination- PCV
Administration Time
Minimum Interval Between Doses
First dose
dose 1-dose 2
dose 2-dose 3
dose 3-dose 4
<6 mos
4 wks
4 wks
8 wks
7-11 mos
4 wks
8 wks
12-24 mos
8 wks
24-59 mos
only one dose vaccination (no further doses needed)
Inactivated poliovirus vaccine (IPV)
Inactive polio virus for poliomyelitis
Combined vacines: DTaP-IPV-Hib, DTaP-IPV
Minimum age: 6 weeks
Routine vaccination: Administration: 0,5 mL im
•Administer a series of IPV at ages 2, 4, 6, and 18 months, with a booster at age
4–6 years
• The final dose in the series should be administered on or after the fourth
birthday and at least 6 months after the previous dose
Catch-up vaccination:
• If 4 or more doses are administered before age 4 years, an additional dose
should be administered at age 4 through 6 years
• Administer a series of OPV (Live –attenuated polio virus) vaccine at ages, 6
and 18 months (For IPV/OPV sequential administration)
• IPV is not routinely recommended for 18 years or older.
Measles, mumps, and rubella vaccine (MMR)
Live attenued viral vaccine (measles, rubella and mumps virus)
Minimum age: 12 months for routine vaccination
Routine vaccination: Administration: 0,5 mL , sc
• Administer the first dose of MMR vaccine at age 12 months, and the
second dose at age 4 through 6 years
• The second dose may be administered before age 4 years, provided
at least 4 weeks have elapsed since the first dose.
Travelling to a measles-endemic region or during an outbreak
•Children aged 6-11 months
• Administer 1 dose of MMR vaccine to infants aged 6 through 11 months
•These children should be revaccinated with 2 doses of MMR vaccine, the first at age 12 and the
second dose at least 4 weeks later.
•Children aged 12 months and older
•The first dose should be administered on or after age 12 months and the second dose at least 4
weeks later.
Catch-up vaccination:
• Ensure that all school-aged children and adolescents have had 2 doses of MMR vaccine; the
minimum interval between the 2 doses is 4 weeks.
Varicella vaccine (VAR)
Live attenued viral vaccine for varicella z0ster
virus (chickenpox)
Minimum age: 12 months
Routine vaccination: Administration: 0,5 mL,sc
• Administer the first dose of VAR vaccine at age 12 months, and the second dose at
age 4 through 6 years (there is no second dose is abcent in «Routine Vaccine
Schedule» in our country
•The second dose may be administered before age 4 years, provided at least 3 months
have elapsed since the first dose. If the second dose was administered at least 4 weeks
after the first dose, it can be accepted as valid
Catch-up vaccination:
• Ensure that all persons aged 7 through 18 years have had 2 doses of varicella
vaccine.
•For children aged 7 through 12 years the recommended minimum interval between
doses is 3 months (if the second dose was administered at least 4 weeks after the first
dose, it can be accepted as valid)
•For persons aged 13 years and older, the minimum interval between doses is 4 weeks.
Hepatitis A vaccine (HepA)
Inactivated viral vaccine for hepatitis A
Minimum age: 12 months
Routine vaccination: Administration: 0,5 mL im
• Initiate the 2-dose HepA vaccine series; separate the 2
doses by 6 to 18 months
• Administer the first dose of Hep A vaccine at 18.month, the second
dose at 24. month (according to Routine Vaccination Schedule in
Turkey)
Catch-up vaccination
• Children who have received 1 dose of HepA vaccine before age 24
months, should receive a second dose 6 to 18 months after the first
dose.
• For any person aged 2 years and older who has not already received
the HepA vaccine series, 2 doses of HepA vaccine separated by 6 to 18
months may be administered if immunity against hepatitis A virus
infection is desired.
• The minimum interval between the two doses is 6 months
General Rules of Vaccination-1
 Vaccines may be given simultaneously on the same day,
whether inactivated or live
 Different inactivated vaccines can be administered at any
interval between doses
 An inactivated and a live vaccine may be spaced at any
interval from each other
 Different live attenuated vaccines (parenteral) if not
administered on the same day, should be given at
least 1 mo apart (because of theoretical concerns about
viral interference)
 Oral live vaccines should be administered simultaneously
or at any intervals before or after live parenteral
vaccines
General Rules of Vaccination-2
 Vaccine doses should not be administered at intervals less
than the minimum intervals or earlier than the minimum
age
 It is not necessary to restart the series or add doses because
of an extended interval between doses intervals
 Preterm infants generally can be vaccinated at the same
chronologic age as fullterm infants according to the
recommeded childhood ımmunization schedule (except
the birth dose of Hep B)
 Hep B vaccination should be deferred in infants
weighing<2 kg at birth until 30 days of age (for child of
HBsAg (-) mother
Vaccine Adverse Reactions
 Local
 pain, swelling, redness at
site of injection
 common with inactivated
vaccines
 usually mild and self-limited
 Systemic
 fever, malaise, headache
 skin eruption
 anaphylaxy
Advers Events For Reporting
 Anaphylaxis or anaphylactic shock (7 days) (all vaccines)
 Brachial neuritis (0-28 days) (for tetanus toxoid containing vaccines-DT, Td,
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TT)
Encephalopathy or encephalitis (7 days) (for pertussis antigen containing
vaccines-DTaP )
Encephalopathy or encephalitis (14 days) (for measles, rubella, mumps virus
containing vaccines-MMR)
Cronic arthritis (42 days) (for rubella virus containing vaccines-MMR)
Trombocytopenic purpura (30 days) (for measles virus or rubella virus
containing vaccines-MMR)
Vaccine strain measles viral infection in an immunodeficient recipient (6
months) (for measles virus containing vaccines-MMR)
Paralytic polio in an nonimmunodeficient recipient (30 days) :Vaccineassociated paralytic polio (VAPP): (for polio live virus containing vaccinesOPV)
BCG-itis (for BCG)
Intussusception (for RV)
Health care professionals report adverse events following vaccination
promptly and accurately to the Vaccine adverse Event Reporting System
(VAERS)
Contraindications to Vaccines
 Anaphylactic reaction to a vaccine component following a prior dose
(For all vaccines)
 Encephalopathy/encephalitis not due to another identifiable cause
occurring within 7 days of pertussis vaccination (For pertussis
vaccine)
 Older than 6 yr of age (For pertussis vaccine)
 Child with progressive neuromotor retardation or convulsions that
can’t be controlled (For pertussis vaccine)
 Severe combined immunodeficiency ( For live vaccines)
 Hospitalized child (For oral polio vaccine)
 Immunocompromised person in household (For polio vaccine)
Vaccine Precautions
•Children who are moderately or severely ill should
usually wait until they recover before getting vaccine
•Had a fever over 105°F after a dose of DTaP
• Had a seizure or collapsed after a dose of DTaP,
•Cried non-stop for 3 hours or more after a dose of
DTaP
Invalid contraindications to vaccination
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Mild illness
Recent exposure to an infection disease
Antimicrobial therapy
History of nonspecific allergies of to a vaccine component
Pregnant person in the household
Breastfeeding
Preterm birth
Allergy to products not present in vaccine or allergy that is
not anaphylactic
 Family history of adverse events
 Family history of sudden infant death syndrome
 Malnutrition
Health care professionals assess for and follow only medically
accepted contraindications
Standards for Immunization Practice
 Vaccination services readily available
 Barriers to vaccination are identified and minimized
 Patient costs are minimized
 Parents and patients are educated about the benefits and risks of
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vaccination
Up-to-date , written vaccination protocols are accessible at all
locations where vaccines are administered
Health care professionals review the vaccination and health status of
patients at every encounter to determine which vaccines are indicated
Health care professionals simultaneously administer as many
indicated vaccine doses as possible
Vaccination records for patients are accurate , complete, and easily
accessible
Systems are used to remind parents and patients, health care
professionals when vaccination are due and to recall those who are
overdue