Ghai Essential Pediatrics8th

weeks prior to delivery, provides passive immunity to the baby due to the transplacental passage of IgG antibodies.

Tetanus toxin is inactivated by formalin to make tetanus toxoid (TT) and adsorbed onto aluminum salts to enhance its immunogenicity. Each dose of TT vaccine contains 5 Lf of the toxoid. The vaccine is heat stable and remains potent for a few weeks even at 37°C. The efficacy of TT vaccinevaries between 80-100%. An antitoxin level of 0.01 JU/ml is considered protective; however, the level of protection available also depends on the toxin load.

Since tetanus may occur at any age, primary immuni­ zation should begin in early infancy. Tetanus toxoid is administered with DT and pertussis (killed or acellular) vaccine in DTP, with 3 doses of the vaccine given 4 weeks apart, followed by boosters at 18 months and 5 yr. DT Td and TT are also available for use in booster immunization at 10 and 16 yr of age and for wound prophylaxis. Previously unimrnunized school children should receive 2 doses of TT 1 month apart. Recommendations for routine tetanus prophylaxis in wound management and indications of tetanus immunoglobulin (TIG) are listed in Table 9.5. TT should not be administered after every injury if immunization is complete and last dose was received within last 10 yr.

Table 9.5: Tetanus prophylaxis following wound

Past doses ofIT	Clean minor wound		All other wounds
	TI	TIG*	TI	TIG*
Unknown or
<3 doses	Yes	No	Yes	Yes
3 doses	No••	No	No•••	No

Use DTwP or DTaP if <7-yr-old and Td or TT in an older child TIG: Tetanus immunoglobulin (250 IU intramuscular)

••Yes if>10 yr since last dose Yes if 5 yr since last dose

Measles Vaccine

Measles vaccine is a live attenuated vaccine. The strain used in India is derived from the Edmonston Zagreb strain of vaccine virus grown in human diploid cell culture. Measles vaccine has a shelf life of 1 yr at 4-8°C, and loses potency rapidly after reconstitution. The vaccine should be reconstituted using sterile precautions and any unused vaccine should be discarded after 4-6 hr since bacterial contamination may lead to staphylococcal sepsis and toxic shock syndrome. Box 9.5 lists standard instructions for its administration.

Maternal immunity may interfere with the immune response to the vaccine during infancy. Administration of the vaccine at 9 months in endemic countries like India balances the need of early protection with the ability to ensure seroconversion. Adequate titers of antibody are generated in 85-90% at 9 months age. In case of an outbreak, vaccine administration as early as 6 months of

Immunization and Immunodeficiency -

	Box 9.5: Measles Vaccine
Dose, route	0.5 ml; subcutaneous
Site	Right upper arm (at insertion of deltoid)
	or anterolateral thigh
Schedule
National Program	At 9 mo ( 6 mo during outbreaks;
	revaccinate 4weeks later, preferably at
	12-15 mo as MMR)
IAP 2012	At 9 mo; administer at least 2 doses of
	measles containing vaccine 4 weeks
	apart; preferably as MMR at 12-15 mo
	and4-6 yr
Catch up <12 mo:	Administer measles vaccine
Catch up 12 mo:	Administer MMR vaccine
Adverse reactions	Fever, transient macular rash ('measles
	like' illness) 5-10 days later

Contraindications (i) Immunosuppressive therapy (e.g. alkylating agents, high dose corticoste­

	roids); (ii) malignancy; (iii) severe
	immunodeficiency (e.g. advanced HN);
	(iv) untreated tuberculosis
Storage	2-8°C; sensitive to heat and light; use
	within4-6 hrs of reconstitution

age may be carried out, with a repeat dose at 12-15 months as part of measles or MMR vaccine.

Post exposure prophylaxis with immunoglobulin is indicated for all immunocompromised contacts irres­ pective of immunization status, and exposed infants aged 6-12 months (see section on Passive Immunization). Unimmunized immunocompetent contacts older than 12 months should receive measles or MMR vaccine within 72 hr of exposure.

Measles Mumps Rubella Vaccine

Most developed countries use a combination of measles, mumps and rubella vaccines rather than measles vaccine alone for primary immunization. Since the occurrence of mumps in adulthood is associated with the risk of oopho­ ritis, some programs recommend the administration of mumps vaccine to all young adults who have not had the disease. Rubella vaccination is mainly directed at preven­ tion of the congenital rubella syndrome and not prevention of primary rubella infection, which is a benign illness.

The mumps component of MMR vaccine has live attenuated mumps virus derived from theJeryl Lynnstrain grown in chick embryo or human diploid cell cultures. Clinical efficacy is 75-90%. The vaccine is safe; there is no association of the vaccine with autism or Crohn disease unlike postulatedpreviously.Aseptic meningitis may occur in 1 in 104 to 105 doses, but is mild and often subclinical. Monovalent mumps vaccine is currently not available in India. Available rubella vaccines are derived from the RA 27/3 strain of the virus grown in human diploid or chick embryo cell culture. The vaccine has a seroconversion rate of over 95% and long lasting immunity, possibly lifelong.

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Adverseeffects followingimmunization are mild (Box 9.6). The vaccine is contraindicated in pregnant women and in immunocompromised persons. However, MMR vaccine is recommended for asymptomatic and symptomatic individualswithHIVifnot severelyimmunocompromised.

Each 0.5 ml dose of the vaccine contains 1000, 5000 and 1000 TCID50 of measles, mumps and rubella, respectively. The vaccine is dispensed as a lyophilized preparation in single and multiple dose. The vaccine should be used within 4 hr of reconstitution to prevent loss of potency. Box 9.6summarisesinstructions forits administration. The vaccine is recommended for use beyond 12-15 months of age because maternal antibodies interfere with response to the vaccine if given earlier. IAP recommends two doses of MMR vaccine, to decrease the risk of primary vaccine failure to the mumps and rubella components.

Haphazard use of rubella or MMR vaccine in children without ensuring optimal immunization coverage may result in an epidemiological shift of disease with more clinical cases in adulthood and a paradoxical increase in congenital rubella syndrome. Hence, the vaccine should be introduced in theNational Program only after ensuring that the routine immunization coverage is at least 80%.

Hepatitis B Vaccine

India has intermediate endemicity for hepatitis B virus (HBV), with about 4% individuals being chronic carriers of the virus. HBV is the leading known cause of chronic hepatitis, cirrhosis andhepatocellularcarcinoma. Infection with HBV may be acquired by the perinatal route (vertical transmission), during childhood through close contact with infected family members (horizontal transmission), through transfusions or use of infected needles and by sexual contact. Infection at younger age is associated with

Box 9.6: Measles, mumps, rubella (MMR) vaccine

Dose, route	0.5 ml; subcutaneous
Site	Right upper arm (at insertion of deltoid)
	or anterolateral thigh
Schedule
National Program	At 15-18 mo (only in some states)
IAP 2012	Two doses at 15 (12-18) mo and 4-6 yr;
	minimum age 12 mo; second dose may
	be given at <4 yr but 24 weeks after the
	first dose
Catch up 212 mo:	Administer 2 doses 24 weeks apart; one
	dose if receivedMMRvaccinepreviously
Adverse reactions	Fever, transient rash, arthralgia, aseptic
	meningitis, lymphadenopathy
Contraindications	(i) Immunosuppressive therapy (e.g.
	alkylating agents, high dose corticoste­
	roids); (ii) malignancy; (iii) severe
	immunodeficiency (e.g. advanced HN);
	(iv) untreated tuberculosis
Storage	2-8°C; sensitive to heat and light; use
	within 4-6 hr of reconstitution

higher risk of chronic carriage and chronic liver disease. In regions of high and intermediate endemicity, vertical and horizontaltransmissions are major modes ofinfection. Hence the WHO recommends universal hepatitis B vaccination in these regions. The Government of India has initiated the incorporation of the vaccine in the National Immunization Schedule in a phased manner.

The current hepatitis B vaccine is a highly purified vaccine produced by recombinant DNA techniques in yeast species and contains aluminium salts as adjuvant. Each pediatric dose of 0.5 ml contains 10 µg of antigenic component. It is recommended that the dose be doubled in adults,patientsonhemodialysis,immunocompromised individuals and those with malignancies. Seroconversion rates are> 95% after three doses. An antibody titre of>10 mIU/ml is considered protective. Box 9.7 summarizes recommendations foradministrationof hepatitisB vaccine. Since immunization at birth prevents horizontal trans­ mission, vaccination should begin at birth if the mother's HBsAg status is not known. Immunization at birth, 1 and 6 months is considered ideal in terms of its proven immunological efficacy. Attempts at integrating the vaccination intotheNational Schedule without increasing number of contacts have led to trials of other schedules which have been found to provide good efficacy. Where birth dose has been missed, it may be given at 6, 10 and 14 weeks of age. Currently, there is no evidence to suggest that booster doses are required.

Hepatitis B surface antigen (HBsAg) screening should be offered to all pregnant women. If the mother is known to be HBsAg negative, vaccination of the child may begin at 6 weeks. Where the mother's status is not known, it is safer to vaccinate the newborn within a few hours of birth. If the mother is known to be HBsAg positive, the child

Box 9.7: Hepatitis B vaccine
Dose, route	0.5 ml (1 ml in adults and in children
	receiving hemodialysis); intramuscular
Site	Anterolateral thigh (deltoid in adults);
	avoid gluteal region
Schedule
National Program	At birth (<12-hr-old), 6 weeks, 14 weeks
IAP 2012	At birth, 6 weeks and 6 mo; may give
	3-4 doses in an alternative schedule*
	while ensuring that (i) doses 1 and 2 are
	24 weeks apart; (ii)doses 2 and 3 are 28
	weeks apart; (iii) final dose is at 26 mo
	of age and 216 weeks beyond first dose
Catch up	Complete 3 doses series; second dose is
	given 24 weeks and third dose 28 weeks
	after previous dose
Adverse reactions	Local soreness; fever; fatigue
Contraindication	Anaphylaxis after previous dose
Storage	2-8°C; do not freeze

*Alternative schedules: (i) birth, 1 and 6 mo; (ii) birth, 6 and 14 weeks; (iii) birth, 6, 10 and 14 weeks; (iv) 6, 10 and 14 weeks

must receive the vaccine within a few hours ofbirth, along with hepatitis B immunoglobulin (HBIG) within 24 hr of birth at a separate site (see section on Passive Immuni­ zation) If HBIG has been administered, any of the schedules incorporating a birthdoseofthevaccinecanbe used. If HBIG is not administered, the baby should be immunizedinan accelerated schedule at0, 1and2 months, along with an additional dose at 9-12 months.

HBIG provides immediate passive immunity and is used in circumstances where an acute exposure to HBsAg positive biological material has occurred. Combined passive and active immunization with concurrent use of HBIG and HB vaccination results in 90% decrease in risk of HBV transmission in circumstances such as needle stick injuries, sexual exposure or use of blood product not screened for HBV (see section on Passive Immunization).

Varicella Vaccine

Chickenpox (varicella) chiefly affects children and young adults in whom it is usually a benign and self limiting infection. The disease may be associated with compli­ cations when occurring in adults, pregnant women and immunocompromised individuals. The available vaccines are live attenuated vaccines derived from the Oka strain of the virus grown in human diploid cell culture. Each dose of the lyophilized vaccine contains at least 1000 plaque formingunits of the attenuated virus. The vaccine elicits both cellular and humoral immune responses and has high (95-99%) protective efficacy. In children above 12 yr, seroconversion rates are 80% with one dose and 90% after two doses. While one dose of the vaccine is sufficient to seroconvert 95% of younger children, two dosesarerecommendedto reducetheriskofbreakthrough infections due to waning immunity.

Varicella vaccine is not included in the National Immunization Program since varicella has less public healthrelevancethan other vaccine preventablediseases, the vaccine is expensive, and ensuring high rates of immunization coverage would be essential to ensure that the disease epidemiology does not shift to affect older individuals, causing severedisease.The IAP recommends the use of varicella vaccine in all children where it is afforded (Box 9.8). It is particularly important to vaccinate children with chronic cardiac or pulmonary disease, HIV infection (while CD4 count is >15% for age), leukemia (during disease is remission with chemotherapy discontinuedfor >3 months)and conditions like nephrotic syndrome where prolonged immunosuppression is anticipated. The vaccine should also be considered in householdcontactsof immunocompromised children, and in adolescents and adults without history of varicella in the past, particularly if staying or working in an institu­ tional setting (e.g. school, hospital or military establish­ ment). Unimmunized household contacts of patients with varicella should receive varicella vaccine within 72 hr but its protective efficacy is uncertain. Varicella zoster

Immunization and Immunodeficiency -

Box 9.8: Varicella vaccine

Dose, route	0.5 ml subcutaneously
Site	Anterolateral thigh or upper arm
Schedule
National Program	Not included
IAP 2012	Two doses at 15--18 mo (minimum age
	12 mo)* and 4-6 yr; second dose may be
	given >3 mo after the first dose
Catch up	Complete two dose series with minimum
	interval of 3 mo between the doses ( 4
	weeks if 12-yr-old)
Adverse reactions	Fever, rash, local pain or redness
Contraindications	Anaphylaxis after previous dose; lympho­
	penia;immunodeficiency; duringimmuno­
	suppressive therapy
Storage	2-8°C; protect from light; use within 30
	min of reconstitution

*Risk of breakthrough infections is lower if given at <!.15 mo

immunoglobulin (VZIG) provides passive immunity to nonimmune individuals who are exposed to varicella and are at significant risk of complications, such as pregnant women, neonates whose mothers have developed varicella 5 days before or 2 days after delivery, and immunocompromised children and adults. These individualsshould receive postexposure prophylaxis with VZIG (5-25 units/kgofbodyweightor12.5 units/kg body weight IV) within 96 hr of exposure.

Typhoid Vaccine

Enteric fever is an important public health problem in India. Threetypesoftyphoidvaccineshavebeendeveloped, with efficacy varying between 50% and 70%.

The whole cell inactivated typhoid vaccines (TA/TAB) were inexpensive vaccines containingheat-killedphenol­ preserved or acetone-inactivated whole cell Salmonella typhi, and S. paratyphi A and B. Two doses of the vaccine, administered subcutaneously 4 weeks apart in children >6-month-old, induced antibodies against the cell wall somatic (0) and flagellar (H) antigens. The vaccine had a protective efficacy of 50-70% but required revaccination every 2-3 yr. The serological response interfered with the interpretationofWidaltest.Adverseeffectswere common, including fever, local pain and malaise. This vaccine is currently not available in India.

The Vi capsular polysaccharide vaccine contains the purified Vi antigen that prevents phagocytosis of S. typhi and inhibits serum bactericidalaction. This unconjugated polysaccharide vaccine elicits anti-Vi antibodies in children above 2 yr and has protective efficacy of 50-75% after 2 weeks of administration. Each dose of the vaccine has 25 µg of the antigen. The IAPCOI recommends its use in all children every 3 yr beginningat 2 yr (Box 9.9). While aVi polysaccharideconjugatevaccinehas beendeveloped,

__E_s_s_e_n_ t_ia_i_P_e_d_ i_a _tr_ic_s_________________________________

Box 9.9: Typhoid Vi capsular polysaccharide vaccine Box 9.10: Hepatitis A vaccine

Dose, route	0.5 ml, subcutaneous or intramuscular
Site	Anterolateral thigh (deltoid in adults)
Schedule
National Program	Not included
IAP 2012	One dose at 2 yr; repeat every 3 yr
Catch up	One dose beyond 2 yr
Adverse reactions	Local pain, swelling, redness; fever
Contraindication	Anaphylaxis after previous dose
Storage	2-8°C; do not freeze

current data on immunogenicity and safety is insufficient to recommend its use.

An oral vaccine has been developed that contains live attenuated bacteria of the Ty21a strain of S. typhi. A

genetically stablemutationmakesit unlikely for thebacteria to revert to a virulent form. The vaccine is available as an enteric capsule containing 2-6 million live lyophilized bacteria that induce intestinal mucosal immunity. Primary immunization, consisting of 3 doses given on alternate days on an empty stomach, has an efficacy of 50-60% within 7 days of completion of the schedule.Sincethebacteriaare inactivated by gastric acidity, capsules must be swallowed intact. Hence, the vaccine is unsuitable for childrenyounger than 6 yr. Antibiotics should not be given between 3 days before to 7 days after the vaccine administration to avoid interference with vaccine 'take'. The vaccine is contra­ indicated in children with significant immunodeficiency. Mild adverse effects include abdominal discomfort and fever. Vaccinationhas to be repeated every 3 yr.Thevaccine is not available in India.

Hepatitis A Vaccine

Infection with hepatitis A virus is endemic in India and is usually benign in children below 5 yr of age, with the majority (50-85%) presenting with minor manifestations like any viral illness. Disease severity, complications and mortality are higherin those with underlying chronicliver disease, adolescents and adults.

The available vaccine contains formalin inactivated viruses grown onhumandiploidcelllines. Each pediatric dose of the vaccine has an antigen content of 720 ELISA units and aluminium hydroxide as an adjuvant. The vaccine has protectiveefficacy of 95-100%.Since maternal antibody may interfere with immune response to the vaccine, the vaccine is avoided in infancy (Box 9.10). A combined vaccine containing hepatitis A and B vaccines may be used in a three dose schedule.

ThehepatitisAvaccineisnotrecommendedforuniversal immunizationsincethediseasespreventedisusuallybenign and of less public health relevance. However, with improvement in hygiene, the infection is increasingly acquired at later ageandmay be symptomatic, sometimes withfulminanthepaticfailure. Hence,IAPreceommeds its administration to all children. The vaccine should

Dose, route	0.5 ml, intramuscular
Site	Deltoid
Schedule
National Program	Not included
IAP 2012	Two doses beyond 1 yr of age, given 6
	mo apart
Catch up	Complete two dose series with interval
	of 6 mo; if 10-yr-old, screen for HAV
	antibody first, administer vaccine only if
	seronegative; use adult vaccine (1440
	units) if 13-yr-old
Adverse reactions	Local pain; nausea, anorexia, malaise
Contraindication	Anaphylaxis after previous dose
Storage	2-8°C; protect from light; use within 30
	min of reconstitution

particularly be considered in children with chronic liver disease who are seronegative for HA virus, children attendingcrechesanddaycarefacilities,travelerstoendemic areas andin adolescentswhoare known tobeseronegative for HA virus. The vaccine is effective if administered to unimrnunizedhouseholdcontactsofpatientssymptomatic with HAV within the last 10 days.

A liveattenuatedvaccinehas becomeavailablein India. Two doses of 1 ml each are administered subcutaneously with an interval of 6 months between the doses.

Rotavlrus Vaccine

Rotavirus is a major cause of diarrhea related morbidity and mortality in children worldwide. Of the 7 known serogroups (A-G), groupA rotaviruses causemosthuman disease. Epidemiologic studies indicate that rotavirus is responsible for 6-45% of diarrheal illnesses requiring hospitaladmissionin Indianchildren.Rotavirusinfections usually affect young infants, and natural infections do not protect against re-infection or severe disease. The first licensed rotavirus vaccine (Rotashield), a live oral tetra­ valent vaccine, waswithdrawnsoon after its introduction in 1998 due to occurrence of vaccine associated intus­ susception. Two live oral vaccines, namely Rotarix and RotaTeq, are currently marketed worldwide.

Rotarix is a monovalent (RVl) live attenuated vaccine containing the human rotavirus GIP (8) strain attenuated by culture in Vero cells. Each dose has at least 106 median cell culture infective dose (CCID50), and is given in orally in a 2 dose schedule (Box 9.11). RotaTeq is a pentavalent (RVS) vaccine consisting of strains reassorted between the bovineandhumanWC3rotavirusescontainingspecificVP7, VP4and/or G6proteins,andattenuatedbyculturein Vero cells. Each dose of thevaccinecontainsa minimum titre of 2-2.8 x 106 infectious units per reassortant and not greater than116 x106 infectiousunitsperaggregatedose,suspended inasolutionofbufferandstabilizer.Itisadministered orally in a three dose schedule at 2, 4 and 6 months.

Box 9.11: Rotavirus vaccine

Dose, route	RVl:1 ml (lyophilized) or1.5 ml (liquid);
	RVS: 2 ml (liquid); oral
Schedule
National Program	Not included
IAP 2012	RVl:2 doses; RVS: 3 doses; at6-14weeks
	c.4weeksapart;maximumage <15 weeks
	for the first dose and <8 mo for the final
	dose; donot begin schedule at ?.15 weeks
Adverse reactions	Intussusception (rare)
Contraindication	Past history of intussusception; severe
	immunodeficiency
Precaution	Postpone vaccination during ongoing
	diarrhea or moderate illness
Storage	2-8°C; do not freeze; protect from light;
	use immediately after reconstitution or
	opening

Intrialsconductedelsewhere,bothvaccineshaveshown 85-98% efficacy against severe rotavirus gastroenteritis and have been demonstrated to be safe with no increased risk of intussusception as compared to placebo. Simul­ taneous administration of rotavirus vaccines with OPV does not appear to affect adversely the efficacy of either vaccine. While efficacy trials in developing countries of Africa and Asia are ongoing, evidence suggests that the efficacyofthevaccinemay be lower incountrieswithhigh ratesofinfectionandcompetitionforintestinalinfectionby other pathogens. However, the morbidity and mortality burden of rotavirus in countries like India is huge and routine immunization with current rotaviral vaccines, despitetheirlower efficacy in these settings, are expected to prevent significant morbidity and mortality. Hence the WHO and IAP endorse routine imminuzation with these vaccines while more efficacious and region specific vaccines are developed.

It is important to adhere to the vaccination schedule. Due to a small risk of intussusception, and the highest risk of rotaviral infections being in early infancy, it is recommended that immunization with current vaccines should be completed by the age of 8 months. Vaccination should be postponed in infants with acute gastroenteritis as it might compromise efficacy of the vaccine. Risks versus benefits of vaccination should be consideredwhile considering vaccination for infants with theoretically increased risk of intussusception, such as chronic gastrointestinal disease and gut malformations.

Haemophilus influenza B Vaccine

Worldwide, Haenwphilus influenza b (Hib) is an important cause of invasive infections like pneumonia, meningitis and bacteremia, especially in children below 2 yr of age. Effectivevaccinesareavailableandtheirincorporationinto the immunization schedule of developed countries has resultedina significantdeclineinmorbidityand mortality attributable to invasive disease due to Hib.

Immunization and Immunodeficiency

The capsular polysaccharide is the moiety used as the antigen in the available vaccines. Since polysaccharide antigensarepoorlyimrnunogenic inchildrenbelow2 yrof age, itisconjugatedtoaproteinantigeninordertoenhance the immunogenicity. The PRP-T vaccine has the tetanus toxoid as the conjugate, the Hb-OC has the mutant CRM 197 diphtheria toxin, while PRP-OMP incorporates the outer membrane protein of meningococcus as conjugate.

PRP-OMP is a more immunogenic vaccine than the other two. Conjugate vaccines for haemophilus influenza con­

tainingdiphtheria toxoid do not contain enough toxoid to be a substitute for DTP or DT.

The IAP-COI recommendsthat Hib vaccine be adminis­ tered to all children; however, given the epidemiological profile of infections with Hib, unirnmunized children above 5 yr of age should not receive the vaccine. Vacci­ nation is particularly recommended prior to splenectomy and in patients with sickle cell disease. Vaccination schedule depends on the age of the child at the time immunizationisinitiated (Box 9.12). Thevaccineissafeand immunogenicandhasaprotectiveefficacyofover95%. The vaccine has been recently introduced as a pentavalent vaccine in somestates in India in the National Program.

Pneumococcal Vaccine

Worldwide, S. pneumoniae is responsible for 15-50% of all episodes of community acquired pneumonia, 30-50% of all cases of acute otitis media and 50% of deaths due to

pneumonia every year. Among 90 known serotypes of S. pneumoniae, 20 serotypes are responsible for 80% of

invasive pneumococcal disease in all ages, while only 13 serotypes account for 75% of disease burden in young children. In India,ithas beendemonstratedthatserotypes 1, 4, 5, 6, 7, 14 and 19 are the most prevalent serotypes causing invasive pneumococcal disease in children. Children below the age of 2 yr are at greatest risk for invasive pneumococcal disease.Theriskforpneumococcal disease is increased in children with congenital immuno­ deficiency, HIV, those on immunosuppressive therapy,

Box 9.12: Haemophilus influenzae b vaccine

Dose, route	0.5 ml intramuscular
Site	Anterolateral thigh
Schedule
National Program	Introduced in some states as pentavalent
	vaccine with DPT and hepatitis B
IAP 2012	Three doses at ?.6 weeks given ?.4weeks
	apart; one booster at15-18 mo
Catch up	At6-12 mo: Two doses ?.8 weeks apart
	with one booster at 15-18 mo; At 12-15
	mo: one dose and one booster at
	15-18 mo; 15-60 mo: one dose; not
	recommended >5-yr-old
Adverse reactions	Fever, rash, local pain or redness
Contraindication	Hypersensitivity to previous dose
Storage	2-8°C

__e_s_esntia_i_P_iedatric s__________________________________

organ transplant recipients, sickle cell disease, asplenia or hyposplenia, chronic cardiac, liver or pulmonary disease (excluding asthma unless on high dose oral steroids), chronic renal failure, nephrotic syndrome, diabetes mellitus and children with cerebrospinal fistula or cochlear implants. Currently, vaccines of two kinds are available, unconjugated polysaccharide vaccine and conjugated vaccines.

The unconjugated polysaccharide vaccine is a 23 valent vaccine (PPV23) containing25 µgofpolysaccharideofeach of 23 serotypes contained in vaccine. Since capsular polysaccharides stimulate B cells directly independent of T cell stimulation, the vaccine is poorly immunogenic

below2 yrandimmunological memory islow. Thevaccine does not reduce nasopharyngeal carriage of S. pneumoniae;

therefore, it does not provide herd immunity. Its efficacy in preventing invasive pneurnococcal disease in the high­ risk population is less than 70%. The vaccine is adminis­ tered intramuscularly in a dose of 0.5 ml; more than two life time doses should not be given.

Pneurnococcal conjugate vaccine (PCV) is available as a 13-valent polysachharide vaccine (PCV13) linked to a

protein carrier and a 10-valent conjugate vaccine (PCVlO) combined with non-typeable Haemophilus influenzae

vaccine. The introduction of conjugated vaccines for routine immunization in developed nations was asso­

ciated with a herdeffect,resulting from reduction in naso­ pharyngeal carriage of S. pneumoniae, causing a significant

decline in pneurnococcal disease in unvaccinated contacts of the vaccines. The antigens in the 13-valent conjugate vaccine are from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F that account for the majority of invasive pneumococcal disease in children. The vaccine has a protective efficacy of 95-99% against invasive pneumococcal disease caused by these serotypes. The current vaccines replace the previously available PCV7 vaccine, which covered only 55% of pneurnococcal sero­ types prevalent in India. Conjugated vaccines with broader serotype vaccines should be available in future.

Since pneurnococcus is a cause of significant morbidity and mortality in children (especially below 2-yr-old), the

IAPCOI recommends the use of the currently available conjugate pneumococcal vaccine (PCV13 or PCVlO) in healthy children aged <2 yr (Box 9.13). Revaccination or further doses after age appropriate primary series with

PCV 13 is not currently recommended. Vaccination of healthy children >5 yr is likely to be associated with less benefits due to the low risk of invasive pneumococcal disease in these children and is not recommended.

All children at high-risk of acquiring the infection or at risk of complications should additionally receive the polysaccharide vaccine, because while PCV provides robust immune response and immune memory, PPV23 provides expanded serotype coverage. Where the cost of PCV is prohibitive, PPV23 alone is given to high-risk children >2 yr of age. If affordable, PCV should be given

Box 9.13: Pneumococcal conjugate vaccines

Dose, route	0.5 ml subcutaneous or intramuscular
Site	Anterolateral thigh
Schedule
National Program	Not included
IAP 2012	Three doses at 2-_6 weeks given 2-_4 weeks
	apart and one booster at 15-18 mo1•2
Catch up	At 7-11 mo: Two doses 2-_4 weeks apart
	and one booster at 15-18 mo; 12-23 mo:
	Two doses2-_8 weeksapart; 24--59 mo: one
	dose; >60 mo: one dose, only if in high­
	risk category
Adverse reactions	Fever, local pain, soreness, malaise
Contraindication	Anaphylaxis after previous dose
Storage	2-8°C; do not freeze

1If primary immunization was with the 7-valent vaccine, administer one dose of the 13-valent vaccine to (i) children 14-59-mo-old; (ii) children 60-71-mo-old and an underlying medical condition.

2Children in high-risk categories should additionally receive the polysaccharide vaccine?.8 weeks after the last dose of PCV vaccine.at at 2 yr of age; revaccinate with polysaccharide after3--5 yr if continue to be at high-risk of infections

first, in the schedule described above; for children over 5 yr a single dose of PCV is recommended. In children aged >2 yr, PPV23 should is given as a single dose. Only one additional dose of PPV23 is recommended in high-risk children; this may be given after 3-5 yr if the child is less than 10 yr of age and after 5 yr if child is aged more than

10 yr.

Human Papillomavirus (HPV) Vaccine

Cervical cancer is the second most common cancer and the leading cause of cancer related deaths in women. The cancerisalmostalwayscausedbypersistentinfectionwith oncogenic human papillomavirus (HPV) belonging to 20 of 100 known serotypes of HPV. Serotypes 16 and 18 are associated with 70% cases of invasive cervical cancer. Oncogenic serotypes of HPV may also cause anal, vulvar, vaginal, penile and oropharyngeal cancers. Nononcogenic HPV serotypes 6 and 11 cause 90% of anogenital warts.

The available vaccines against HPV are self-assembling virus like particles (VLP) constituted of recombinant Ll, themajorcapsidproteinof HPV. Sincethesedonot contain any nucleic acid, these empty capsids are noninfectious but capable of eliciting a host immune response. VLP basedvaccinespreventmore than 90% newinfectionswith the serotypes included in the vaccines. The vaccines do not protect against serotypes with which infection has already occurred before vaccination.

Two vaccines are currentlylicensed. Gardasil (HPV4) is a quadrivalent vaccine active against HPV strains 6, 11,

16 and 18 and Cervarix (HPV2) is a bivalent vaccine targeting only HPV 16 and 18. Clinical trials with both vaccines have shown good efficacy against types 16, 18 related cervical in situ neoplasia grades 2 and 3 and

adenocarcinoma in situ. Gardasil is also effective in preventing vaccine type related genital warts, vaginal intraepithelial neoplasia and vulvar intraepithelial neoplasia. Both vaccines are highly immunogenic and persistent protection for up to 5 yr has been demonstrated. There are no serious adverse events associated with HPV immunization.

The vaccine is of public health importance in a country like India where compliance with routine screening for cervical cancer is low and several women are diagnosed with the cancer every year. However, the duration of protectionprovided andhence,theidealageatvaccination and need of booster doses, if any, remain tobe determined. The vaccine is not expected to be effective in women already persistently infected with the virus. Any cross protection against other strains is likely to be modest. Socioculturalissuesrelatedto the vaccine being protective against a sexually transmitted disease may limit its acceptability. Importantly, immunization status should not create a false complacency resulting in a decline in routine screening for cervical cancer, especially when routine immunization has not been ensured, because this may result in a paradoxical rise in cervical cancer related mortality. Screening programs should therefore continue as per recommendations.

The IAPCOI recommends that the HPV vaccines should be offered to all girls who can afford the vaccine, given priortosexualdebut, as acervicalcancerpreventing vaccine and not asa vaccineagainst asexuallytransmitted infection (STI). The recommended age for initiation of vaccination is 10-12 yr, with catch up vaccination permitted up to 26 yr of age (Box 9.14). Both vaccines are contraindicated in patients with history of hypersensitivity to any vaccine and should be avoided in pregnancy. The vaccines may have a lowerirnrnunogenicity andefficacy inirnrnunocomprornised hosts. At present boosters are not recommended.

Japanese B Encephalitis Vaccine

Japanese encephalitis is an important cause of viral encephalitis in our country; being responsible for 2000-

Box 9.14: Human papillomavirus vaccine

Dose, route	0.5 ml intramuscular
Site	Upper arm (deltoid)
Schedule
National Program	Not included
IAP 2012	Girls 11-12 yr old (minimum 9 yr*)
	HPV4: At 0, 2 and 6 mo; HPV2: 0, 1 and 6
	mo)
Catch up	Before initiation of sexual activity
Adverse reactions	Local pain, swelling, erythema; fever
Contraindication	Anaphylaxis after previous dose
Storage	2-8°C; protect from light

* HPV4 may be given to boys as well

Immunization and Immunodeficiency -

3000 cases and 500-600 deaths annually. In absence of specific therapy, vaccination remains the most important control measure and is indicated in all children between 1-15 yr of age residing in highly endemic areas like Andhra Pradesh, Uttar Pradesh and Karnataka. It should also be given to visitors to endemic areas if duration of stay is expected to be more than 4 weeks. Three types of vaccineare available, themousebrain-derived inactivated vaccine, the cell culture-derived inactivated vaccine and the cell culture-derived live attenuated vaccine.

The mouse brain-derived vaccine is an inactivated vaccine administered subcutaneously in a dose of 0.5 ml for children between 1-3 yr and 1 ml in an older child. Primary immunization consists of 3 doses; the second and third doses are given 7 and 30 days after the first dose. Booster doses are administered at 1 yr after primary immunization and every 3 yr subsequently. Common adverse events include fever, malaise and local tenderness and redness. Reports of a temporal relationship of vaccination to acute encephalitis and anaphylactic reactions in recipients have resulted in decline in usage of this vaccine. An inactivated vaccine derived from primary hamster kidney cell line was popular in China, but its use was discontinued following availability of the live cell culture derived vaccine.

The cell culture derived live attenuated vaccine is the preferredvaccine inIndia. The vaccine is based ona stable neuro-attenuated strain of JE virus, the SA-14-14-2, and was first used in China and subsequently elsewhere in Asia. Studies demonstrate that the protective efficacy of on dose of the vaccine is 98-99% (Box 9.15). The vaccine has been used since 2006 in campaigns in hyperendemic districts of Uttar Pradesh, West Bengal, Assam and Karnataka.

Influenza Vaccines

The influenza virus has three antigenic types (A, B and C) and several subtypes (based on the surface antigens hemagglutinin and neuraminidase), with frequent mutations due to antigenic drifts and antigenic shifts, resulting in frequent changes in the strains in circulation. Since the available vaccines elicit a strain specific hurnoral immune response, this is the only vaccine whose

Box 9.15: Japanese B encephalitis vaccine

Dose, route	0.5 ml subcutaneous
Site	Anterolateral thigh or upper arm
Schedule
National Program	Only in endemic areas; one dose at 9 mo
	(minimum age 8 mo)
IAP 2012	Only in endemic areas
Catch up	One dose in susceptible children up to
	15-yr-old (during disease outbreak or in
	campaign)
Adverse reactions	Fever, malaise

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composition has to be altered yearly according to the expectationof the prevalent strain inthe next peak season.

Influenzavaccinesareinactivated vaccinesderivedfrom viruses grown in embryonated hen's eggs and are of three types. Wholevirus vaccines that were availablepreviously were associated with significant adverse effects, especially in children; hence they are no longer used. Split product vaccines are produced from detergent treated highly purified influenza viruses. Surface antigen vaccines are subunit vaccines containing the purified antigens hem­ agglutinin and neuraminidase. Current vaccines are highlyimmunogenic and associatedwithminimaladverse events. The vaccines are usually trivalent, containing two influenza A subtypes and one influenza B strain. The composition of the vaccine is reviewed by the WHO six­ monthlytoupdateantigenscontainedinthevaccinebased on the prevalent circulating strains. The vaccine is recommended for use in high-risk children, including thosewithchronic cardiac orpulmonarydisease, immuno­ deficiency, HIV infection, sickle cell disease, diabetes mellitus, systemic lupus erythematosus, longterm aspirin therapyand children with severe asthma who require oral corticosteroids. Recommendations for administration are listed in Box 9.16.

Meningococcal Vaccine

Neisseria meningitidis is a major cause of bacterial meningitis accounting for 30-40% of cases in children below 15 yr. Endemic cases and severe meningococcal disease are primarily seen in children and adolescents; attackrates arehighestininfantsbetween3 and 12months of age. Even with treatment, case fatality rates are high (5-15%). The infection is usually due to serogroups A, B, C, Y and W135; serogroupA (andsometimesC)may cause epidemics.In India endemic cases are chiefly due to sero­ group B.Infection resultsin serogroup specific immunity.

Two types of vaccines have been developed: the unconjugated polysaccharide vaccines and a conjugate group C vaccine. Unconjugated vaccines contain group specific capsular polysaccharides, which, like other polysaccharide vaccines, are T cell independent and do

Box 9.16: Inactivated influenza vaccine

Dose, route	0.5 ml (0.25 ml <3 yr); intramuscular
Site	Anterolateral thigh or upper arm
Schedule
National Program	Not included
!AP 2012	Only in high-risk categories
	First time vaccination: Two doses 4
	weeks apart if 6 mo to 9-yr-old and one
	dose if >9 yr; annual revaccination with
	one dose; best administered before rainy
	season
Adverse reactions	Local pain, redness; anaphylaxis
Contraindication	Anaphylaxis after previous dose
Storage	2-8°C; do not freeze

not induce immunological memory and are not very immunogenic below 2 yr of age. Bivalent (containing group A and C) and tetravalent (containing groups A, C, Y and W135) vaccines are available.

Themeningococcal vaccineis indicated in close contacts of patients with meningococcal disease (as an adjunct to chemoprophylaxis),certainhigh-riskgroups (complement deficiency, sickle cell anemia, asplenia, before splenec­ tomy), during disease outbreaks (when caused by a serogroup included in the vaccine) and before travel to the high endemicity belt in Africa.

The vaccine is administered as indicated in Box 9.17. If required, revaccination is considered after 3-5 yr. The vaccine is not recommended for universal immunization in India. During epidemics, children above 2 yr of age may be administered the vaccine, particularly close household contacts.

The conjugated group C vaccine has been marketed in some countries where group C is themost commonisolate in meningococcal disease. Three doses of the vaccine are administered 4-8 weeks apart in children below 6 months, while 2 doses suffice for 6-12 months age and 1 dose is enough in older children.

Box 9.17: Meningococcal vaccine

Dose, route	0.5 ml subcutaneous or intramuscular
Site	Anterolateral thigh or upper arm
Schedule
National Program	Not included
IAP 2012	Single dose in high-risk categories older
	than 2 yr; repeat after 3-5 yr if required
Adverse reactions	Fever, local pain or redness
Contraindication	Anaphylaxis after previous dose
Storage	2-8°C; protect from light; use within 30
	min of reconstitution

Rabies Vaccine

Rabies is endemic in India, accounting for 50% of global mortality associated with the disease. The previously availablenervetissuevaccinesarenolongerrecommended due to poor efficacy and high incidence of adverse effects, like neuroparalytic reactions. Three types of vaccines are available against the virus. The purified duck embryo vaccine (PDEV), available for several decades, isfreefrom myelin basic protein, is safe and its immunogenicity is comparable to modern tissue culture vaccines. Modern tissue culture vaccines includepurifiedchickembryo cell (PCEC) vaccine (Rabipur), human diploid cell vaccine (HDCV) (Rabivax) and purified vero cell vaccine (PVRV) (Verorab,Abhayrab); these vaccines have similar efficacy and safety. The vaccines are available as lyophilized products that are reconstituted before use. The WHO requires each cell culture vaccine to have a potency of at least 2.5 IU per intramuscular dose.

Following an animal bite, the wound should be immediately irrigated with running water for 10 min,

cleaned thoroughly with soap and coated with povidone iodine, 70% alcohol or tincture iodine. All patients with wound category III (WHO recommendations) should receive rabies immunoglobulin (RIG), including trans­ dermal bites or scratches and contamination of mucous membranes with saliva (e.g. licks). RIG is not required in caseoflicks onintactorbroken skin, nibbling ofuncovered skin and minor scratches or abrasions without bleeding. Wound suturing should be avoided; if essential, suturing is postponed till after administration of RIG.

RIG provides passive immunity by neutralizing the rabies viruses, thus preventing neural infection.The dose of RIG is 20 U/kg for human (HRIG) and 40 U/kg for equine (ERIG) immunoglobulin.RIG should be infiltrated in and around the wound; in case of large or multiple wounds, RIG may be diluted with normal saline so as to infiltrate all wounded areas. Any remaining immuno­ globulin is administered intramuscularly at a site away fromvaccinesite,usuallythedeltoidor anterolateral thigh. HRIG is expensive and not widely available. ERIG is associated with a high-risk of adverse effects including anaphylaxis, and requires skin testing prior to its use.

The victim should receive postexposure prophylaxis with rabies vaccine by the intramuscular and intradermal route. The anterolateral thigh and deltoid region are pre­ ferred sites for intramuscular administration; the gluteal region should not be used.The dose is 1 ml for all modern tissueculturevaccines except PVRV in which casethedose is 0.5 ml. The intradermal dose is one-fifth of the intra­ muscular dose. Local pain, swelling or induration are common; less commonly, systemic symptoms may be noted,suchas fever, malaise, abdominalpainor headache. The most commonly used schedule for administration is

the Essen Schedule or WHO Standard Schedule, in which the vaccine is administered intramuscularly on days 0, 3, 7, 14 and 30.An additional dose on day 90 is recommended in immunocompromised or severely malnourished individuals.The Zagreb Schedule (two doses on day 0, a dose each on days 7 and 14) induces an early immune response, is now approved for use in India, using either PCEC or PRY, in centers with adequate training and frequent use of the vaccine. "The Thai red Cross Schedule involves administration of two intradermal doses each on days 0, 3 and 7 and one dose each on days 28 and 90.

Pre-exposure prophylaxis is offered to individuals at high-risk of rabies due to contact with animals, e.g. veterinary doctors, wildlife workers, dog handlers, taxidermists, postmen, animal laboratory workers, municipal workers, etc. Three doses are recommended to be given intramuscularly on days 0, 7 and 21 or 28. A boosterdoseisrequiredafter1yrandevery5yrthereafter. Incaseofre-exposureaftercompletedpreorpost-exposure prophylaxis,twodosesarerecommendedondays O and3. The intradermal schedule using MTCV is also acceptable; here the boosters are required yearly. Since HRIG is required in addition to the vaccine for most animal bites

Immunization and Immunodeficiency -

and the availability, cost and knowledge regarding use of HRIG is limited, pre-exposure prophylaxis against rabies should be offered to all children at high-risk for rabies.

Combination Vaccines

With the availability of vaccines against several diseases, achildneedstobeadministeredmorethantwentyantigens in the first two years. A combination vaccine consists of multiple immunogens physically combined in a single preparation, includingantigens or serotypes of the same pathogen (e.g. trivalent polio vaccine) or different pathogens (e.g. DTP vaccine).The conceptisdistinct from simultaneous administration of multiple physically separate vaccines at the same time at separate sites or by different routes. Studies indicatethattheimmune system of an infant can respond to a large number of antigens simultaneously, and that the efficacy of currently recommended vaccines isnot altered by their concurrent administration, if recommended to be given at the same age.Combiningvaccineshasseveralbenefits. Thenumber of injections at each visit is decreased and fewer visits are required, leading to increased compliance and enhanced immunization coverage. Benefits to the immunization programincludedecreased requirement ofstoragespace, decreased expenditure on packaging and transportation, andsimultaneousvaccinationagainstseveraldiseasesfor children who have missed previous doses.

However, there are several challenges in the develop­ ment of combination vaccines. The antigens combined togetherin avaccineshouldbe compatiblewitheachother, should not interfere with each other's immunological 'take' (relevant especially for live viral vaccines) and shouldbe indicated at the sametime.Some antigens may require an adjuvant to be present in the combination. The total volume of the vaccine should not be excessive and the product should be stable for at least 18-24 months. Before recommending a particular combination vaccine, its efficacy is evaluated in clinical trials and cost benefit analyses. Combination vaccines in common use include DTwP, DTaP, DT, dT, OPV, IPV, MMR and influenza vaccines. Other trivalent, quadrivalent or tetravalent combination vaccines that are available in India and abroad are listed in Table 9.6. Some vaccines are not available as combination vaccines but may be combined in the same syringe of permitted by the manufacturer, as indicated in the table.

VACCINE ADMINISTRATION

Standard precautions should be followed to minimize the risks of spreading infections during the administration of vaccines, including attention to hand washing, safe disposal of needles and vaccine vials and appropriate management of needlestickinjury.Vaccineadministrators should inspect the vaccine and diluent vials for the date of expiry, storage conditions and appearance.

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_

Vaccine

dTaP DTaP-Hib-IPV DTwP DTwP-HB DTwP-HB-Hib

DTaP-Hib

DTwP-Hib

HepA-HB

Meningococcal

Pneumococcal

Table 9.6: Combination vaccines for use in children and infants

Example

Boostrix®, Adacel® Pentaxim®

Multiple brands, e.g.Tripvac®, Triple antigen®, Comvac3®

Multiple brands, e.g. Shantetra®, Q-VAC®, Tritanrix-HB®, Tripvac-HB®, Comvac-4-HB® Multiple brands, e.g. Easy-5®, Pentavac®, Comvac-5®, Shan-5®

May combine vaccines if permitted by manufacturer, e.g. Qvac®+HibPro®, Hiberix®+Tratanrix® May combine Tripacel®+ActHib®, Infanrix®+Hiberix®

Multiple brands, e.g. Easy-4®, Quadrovax®, Shan-4®, TetractHib®; Triple antigen®+HibPro® Twinrix®

A, C, Y and 135 (Mencevax ACWY®); A, C, Y and 135 DT conjugate (Meningococcal A & C®) 7 valent (Prevnar®), 23 valent (Pneumo23®), polyvalent polysaccharide (Pneumovax®)

Combination vaccines licensed elsewhere but not in India (common brands)

DTaP-HB (Tritanrix®), DTaP-HB-IPV (Pediatrix®), DTaP-HB-IPV/Hib (Infanrix hexa®), dT-IPV, DTaP-IPV (Quadracel®) Hib--HB (Comvax), Hib-DT (Vaxem HIB®), Hib-TT conjugate (ActHIB®), Trivalent Hib type A, B, split virion (Vaxigrip®) HepA-Typhoid (Hepatyrix®); MMR + varicella (Priorix tetra®, Proquad®)

Combined ACW135Y polysaccharide meningitis (ACWY Vax®)

Vaccines available as lyophilized powder may require to be reconstituted in (i) sterile or distilled water, e.g. vaccines against measles, mumps,rubella (with or without varicella), meningococcus (MPSV4), rabies (HDCV, PCECV), varicella or zoster; (ii) normal saline, e.g. Hib vaccine; or (iii) another vaccine, e.g. combination vaccines combining DTaP, polio and Hib vaccines (the diluent containsthe DTaP-IPVvaccine)and tetravalent meningo­ coccal vaccine (the diluent contains MenCWY vaccine). The maximum time allowed between reconstitution and use varies from within 30 min (DTaP-IPV-Hib, MMRV, Hib with MenCY, rabies, varicella and zoster), to 8 hr (MMR, MCV4) or 24 hr (Hib, rotavirus vaccines). The reconstitutedvaccineshouldnot be used ifthereis discolo­ ration, extraneous particulate matter and obvious lack of resuspension of the lyophilized powder.

Anxiety and pain are commonly associated with vaccination. Some evidence-based strategies used to reduce these include: (i)theuseofantipyretics to ease pain; (ii) age-appropriate nonpharmacologic distraction techniques (reading books, playing music, pretending to blow away the pain, deep breathing); (iii) breastfeeding or ingestion of sweet-tasting liquids before or during vaccination; (iv)administering the mostpainfulvaccine (e.g. MMR, PCV or HPV) last; (v) stroking the skin near the injection site; (vi) administering intramuscular injections rapidly without aspiration; and (vii) the use of topical analgesia (e.g. 5%lidocaineorprilocaine emulsionor spray). Other techniques that may lessen anxiety in older children areexplainingthe procedure, andadministeringthe vaccine in the sitting position rather than lying down.

Adverse Events following Vaccination

Anadverseeventfollowingimmunizationisanyuntoward effect observed after vaccination, and may be categorized as follows: (i) Vaccine-induced: Event is caused by the

vaccine or the individual's response to its administration, and would not have occurred without vaccination, e.g. vaccine-associated paralytic poliomyelitis, BCG related adenitis or encephalopathy following DPT; (ii) Vaccine­ potentiated: Events that are precipitated by vaccination but mayhaveoccurredwithoutvaccination,e.g.thefirstfebrile seizure in a predisposed child; (iii) Programmatic error: An event caused by technical error in vaccine preparation, handling oradministration,e.g.toxicshocksyndromedue to bacterial contamination of measles vaccine; and (iv) Coincidental: An event that is temporally linked to the vaccination but is expected to have followed vaccine administration only by chance ordue to unrelated illness.

Common events following vaccination include fever, irritability and swelling and redness at the injection site. These are self limiting or may require the use of cool compresses or paracetamol. Immediate-type allergic reactions to vaccinesarerare anddifficulttopredict.Severe reactions (e.g.anaphylaxis)are usually IgEmediated,occur in response to vaccine constituents (rather than microbial contamination) and usually appear within minutes. While anaphylaxis may follow administration of any vaccine, the most commonly implicated are the vaccines against yellow fever, MMR and tetanus. Since symptoms may sometimes bedelayed,eachchildshouldbeobservedforatleast 15 min after vaccine administration. It is important to distinguish anaphylaxisfromvasovagalreactionfollowingvaccination. Prior history of syncope with painful stimuli and the presence of pallor and bradycardia, rather than flushing and tachycardia (seen with anaphylaxis) suggest syncope rather than anaphylaxis.

When evaluating for a possible vaccine allergy, one should consider the timing of reaction and history of previous exposure to the vaccine. If a repeat dose of the same or similar vaccine is considered necessary, the child should be evaluated by a dermatologist for the need for a