CONUNDRUM OF IMMUNISATION

IN NEPHROTIC SYNDROME

DR. VINO D CH O UDH A RY , D N B ( P E D ) , F I S P N , F P N ( T N M G R U )

SENIOR REGISTRAR
DEPARTMEN T OF PEDIATR IC NEPHRO LO G Y
DR MEHTA’ S CHILDR E N,S HOSPITAL

WHY CONUNDRUM?
• Steroids and immunosuppressive medication
• Concerns regarding efficacy and safety
• Possibility of relapse
• Lower seroconversion rates
• Flare up the disease

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OVERVIEW
• VACCINES
• VACCINE IMMUNOLOGY
• CHILDREN ON STEROIDS
• CHILDREN ON IMMUNOSUPPRESIVE AGENTS
• RECOMMENDATIONS- INDIVIDUAL VACCINES

THE VACCINES - INACTIVATED

Component Disease protection
Protein Killed/subunits/cell Pertussis (whole cell / acellular)
components Polio (Salk)
Hepatitis B, Hepatitis A
Influenza, Papilloma virus
Japanese encephalitis
Rabies
Toxoid Diphtheria
Tetanus
Conjugated Haemophilus influenza type B
Pneumococcal
Meningococcal
Typhoid
Polysaccharide Pneumococcal
Meningococcal
Haemophilus influenza
Typhoid

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THE VACCINES - LIFE
Component Disease protection
Live attenuated Rotavirus
MMR
Varicella
Influenza
Polio (Sabin)
Hepatitis A
Typhoid
Yellow fever
Japanese encephalitis

Live mycobacterium BCG

VACCINE IMMUNOLOGY
• Produce specific antibody within 2-4 weeks
• IgM followed by IgG
T-CELL DEPENDENT VACCINES
(protein vaccine, conjugate vaccine, and live attenuated vaccine)
↓
Greater antibody response with persistence of antigen
↓
Induce immunological memory
↓
Boosting of IgG levels within 4-7 days upon subsequent booster dose

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VACCINE IMMUNOLOGY
• T-CELL INDEPENDENT VACCINES (Polysaccharide)
• Revaccination- same or lower effect than primary dose

Directly stimulate conversion of B lymphocyte

↓
Specific IgM and IgG producing plasma cells

• Inability to induce immunological memory & low avidity of antibodies

• Lack of efficacy in ˂2 yrs of age

CHILD WITH NS ON IMMUNOSUPPRESSIVE AGENTS

• Cyclophosphamide and chlorambucil - alkylating agents that inhibit DNA
replication in lymphocytes, leading to cell death
• Mycophenolic acid inhibits both T- and B-lymphocyte proliferation by inhibiting
inosine monophosphate dehydrogenase
• Calcineurin inhibitors (CSA and TAC) inhibit interleukin dependent growth and
differentiation of activated lymphocytes
• RTX, a chimeric monoclonal antibody, acts by inhibiting CD20- mediated B-cell
proliferation and differentiation

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IN GENERAL
• Prednisolone ≥ 2mg/kg or ≥ 20mg daily or alternate days for >14 days are
considered to be IS and should not receive live vaccines
• In patients on intermittent immunosuppression with steroids alone,
vaccinations may be delayed until the child is in remission, off steroid therapy,
or on the lowest possible dose
• Delay live vaccination until the child is off steroids for 1 month
• In children on long-term steroids only, live vaccines may be given when the
dose is tapered down to a low dose, alternate day schedule
• Inactivated vaccines can be safely given for children on steroids and should not
be delayed.

PNEUMOCOCCAL VACCINE- EVIDENCE

STATUS
NS on steroids only
NS on Immunosuppression
EVIDENCE
• Initial studies: rapid decline in antibody titres
Ayfer ped nephrol 2004 (n=9)
• Recent studies: equally effective if given in relapse or
remission
Ulinski ped nephrol 2008 (n=30)
• PCV7: (n=15) adequate response was maintained at
12-14months, no IPD case in 18 months
Liakou vaccine 2011 & 2014
• Reduced immune response (94-100%) (n=18)
Liakou vaccine 2011 & 2014

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PNEUMOCOCCAL VACCINE- EVIDENCE

• N=42
• First study to PCV13
• High antibody titre after 1 year
• No change in relapse frequency

PNEUMOCOCCAL VACCINE- RECOMMENDATION

AGE VACCINE DOSAGE COMMENTS
HISTORY
<2 years No prior PCV 13 ONLY Primary dose given at 1 to 2
vaccination • 6wks-6mth- 3D+1B month intervals and booster
• 7mth-11mth- 2D+ 1B after 1 year
• 12mth- 23 mth- 2D
24-71 months Previously PCV 13- 1D + PPV23-1D Minimum gap of 8 weeks
vaccinated • >5years –PPV23 as 1 B between PCV 13 and PPV23
Previously PCV 13- 2D + PPV23-1D
unvaccinated • >5years –PPV23 as 1 B
or incompletely
vaccinated
>6 years PCV 13- 1D + PPV23-1D

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INFLUENZA- EVIDENCE
STATUS EVIDENCE
NS on steroids only 80% achieved protective titres after vaccination (n=19), level similar
to controls, persisted in 50% at 6 months.
Poyrazoglu et al ped nephrol 2004

On immunosuppression In SLE: response similar to controls

Aikawa Lupus 2013

On immunosuppression Antibody acquisition after vaccination was favorable, and no

adverse events occurred in pediatric patients with renal disease
receiving concomitant steroid and immunosuppressant therapy
Tanaka vaccine 2015

INFLUENZA- RECOMMENDATIONS
• Recommended age >6 month of age
• First time vaccination: 6month-9yrs- two doses 1 month apart
• Should be given yearly
• Doses: 6 month- 3 yrs is 0.25ml; >3yrs is 0.5ml
• Inactivated vaccine only
• Household contacts
• Contraindicated if severe allergy to chicken or egg protein

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HEPATITIS B- EVIDENCE
STATUS EVIDENCE
CKD Pre-dialysis response is better.
20mcg recombinant vaccine×3 doses, seroprotection rates
Predialysis: 100%
Dialysis: 94%
SW PN Study group AJKD 2002

NS on steroids only 76% had protective antobody titre

(titre higher if immunised prior to NS onset)
Mantan ped nephrol 2013

NS on immunosuppression 37% had protective antibody

Mantan ped nephrol 2013

HEPATITIS B -RECOMMENDATIONS
• Suboptimal response, rapid decline of antibody titre

Increased dose(40mcg in adult and 20mcg in children) or

Increased no. of doses- 0,1,2,12 months
• Official guideline – not changed

3 doses at 0, 6 week, and 6 months (10mcg <18 yrs; 20 mcg > 18yrs)

HBV surface antibody titre should be checked after 1 month of dose completion
↓
If titre < 10mIU/ml
↓
Test for hepatitis carrier status
↓
If negtive repeat three doses course

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VARICELLA- EVIDENCE
STATUS EVIDENCE

CKD 85-88% seroconversion with 1 dose

98-100% with 2 doses
SW ped nephrol group 2003

NS on Steroids 85% after 1 dose, 100% after 2 doses

Antobodies detectable after 2 years
Alpay et al, ped nephrol 2002

NS on immunosuppression Not reported

VARICELLA- RECOMMENDATIONS
• Avoid in immunosuppression
• In SSNS- give once off steroid for 4 weeks or on low dose alternate day therapy
(<0.5 mg/kg /day)
• VZIG within 72 hrs of exposure
• Acyclovir for clinical disease

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OTHERS
• MENINGOCOCCAL:

Tetravalent conjugated vaccine (A/C/Y/W-135:Menactra)is preffered

Minimum interval between two doses- 8 weeks

• HAEMOPHILUS INFLUENZA TYPE B:

4 doses (if younger than 2 years)

1 dose (if older than 2 years)

• JAPANESE ENCEPHILITIS:

Recommended for endemic areas

RABIES
• Wound cleansing
• Human rabies immune globulin (HRIG)@20 IU/kg body weight. Infiltrate HRIG
into and around wound. Remaining HRIG given IM at a site distant from the
vaccination site.
• Rabies vaccine: Five 1.0 mL doses, given IM
• Adults/older children: deltoid area
• Young children: anterolateral thigh
• Never in gluteal region

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DEFERMENT OF IMMUNISATION

IMMUNOSUPPRESSION NO VACCINATION WITHIN

Pulse steroids 3 months
Rituximab (depletion of B-cells for 2-11 1 year
months: median 6 month)
High dose 11 months Killed vaccine can
IVIG If live vaccine be given but
Low dose 3- 4 months unknown
response

HOUSEHOLD CONTACTS
• Close contacts –family /siblings

• Influenza, pertussis, HBV

• Contraindication:

Absolute: OPV & Rotavirus (can be transmitted)

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TAKE HOME MESSAGE
• Vaccination does not cause relapse of Nephrotic syndrome

• Vaccination is effective on doses of prednisolone of less than 20mg/m2/day

• Immunise at least 4-8 weeks before potent immunosuppression

THANK YOU

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