Typhoid Vaccine …… Single Dose ….. Lifelong Immunity TYPHOID VACCINATION  : WHO Guidelines 2018 Life long Imuunity : 85 %

1. Typhoid Vaccine ……
Single Dose …..
Lifelong Immunity
Dr. Sharda Jain / Dr Jyoti Agarwal

2. Life long Imuunity : 85 %
TYPHOID VACCINATION
: WHO Guidelines 2018

3. This position paper published in March 2018 replaces the
WHO position paper on typhoid vaccines published in
2008.
It re-emphasises the importance of vaccination to control
typhoid fever and presents the WHO recommendations on
the use of a new generation of typhoid conjugate vaccine.

4. WHAT IS TYPHOID FEVER?
• Result of systemic infection caused by S. typhi ,paratyphi
• Clinically characterized by typical,gradual continuous fever
for 3 to 4 weeks.
• Relative bradycardia with involvement of intestinal lymphoid
tissues, reticulo-endothelial system & gall bladder
• May occur sporadically, epidemically or endemically
• Found only in human
Source: Ajay Kalra, Vipin M. Vashishtha. 3.11 TYPHOID VACCINES. IAP Guidebook on Immunization 2013–14. page no 257-270

5. GLOBAL BURDEN OF ENTERIC FEVER
Most common etiological
sources of bacteremia in
many developing
countries, with most of the
cases originating in the
Indian subcontinent of
South Asia.
Source: Ajay Kalra, Vipin M. Vashishtha. 3.11 TYPHOID VACCINES. IAP Guidebook on Immunization 2013–14. page no 257-270

6. TYPHOID FEVER : 2 CRORE CASES
: 2 LACS DEATHS

7. Proprietary and confidential — do not distribute
BURDEN OF TYPHOID IN INDIA
• Recent systematic review: Incidence of typhoid in India at approx 3.4 million
cases, which would account for approx 30% of the global burden.1
• High burden in the subcontinent is further compounded by a high prevalence of
antimicrobial resistance in typhoidal Salmonella.1
Significant morbidity & mortality reported in India due to typhoid fever
20162 20173 20183
Cases Deaths Cases Deaths Cases Deaths
Males 1186573 304 1211346 304 1239310 230
Females 1029232 207 1053107 192 1069227 169
Total 2215805 511 2264453 496 2308537 399

8. USA :300/YEAR TRAVELERS
>80 % TYPOID ,>90 % PARATYPHOID

9. A . Global Burden  11 and 21 million cases ( 2 crore )
Deaths approximately 1.5 to 2 lacs deaths annually( 2 % )
B .Children are disproportionately affected by typhoid
fever, with peak incidence known to
occur in individuals aged 5 to <15 years of age.
TYPHOID FEVER:
Challenges

10. C .MDR typhoid Fever (MDRTF) in the last
15 years : India
• Incidence of MDRTF : Increased from 35% in
1999 to 66% in 2005
• Mortality during MDRTF epidemics increased
7% to 16% (Much higher than seen in
susceptible typhoid fever 2%)
• Increased incidence of Complications

11. Proprietary and confidential — do not distribute
D. Challenges  MDRTF
The emergence of antimicrobial resistant
strains of S. Typhoid .
USA : resistant to fluroquinolone Antibiotics
Trends over the past few decades and recent
outbreak of ceftriaxone-resistant typhoid in
Pakistan demonstrate the importance of
understanding local resistance patterns to
enable the selection of appropriate antibiotics.

12. TREATMENT
• PROMPT Rx  prvents complication & case
fatality rate <1 %
• Local susceptility of drug to S.typhi &
S.paratyphi --.tobe known.
• FLUOROQUINES MOST EFFECTIVE
CURE RATE 98% .,RELAPSE RATE <2 %
Ciproflox , ofloxacin

13. TREATMENT
AS RESISTANCE IS COMMON IN
INDIA
CEFTRIAXONE /CEFOTAXIME /CEFIXIME or
AZITHROMYCIN
Or high dose of CIPROFLOX 70 mg BD FOR 10-
14 DAYS

14. WHICH OF THE FOLLOWING IS ACCURATE
REGARDING TREATMENT OF
TYPHOID FEVER?
• Treatment should be initiated only after confirmatory tests
• Cholecystectomy is almost always successful in eradicating
the carrier state
• Uncomplicated typhoid fever should be treated with
ciproflox .
Ceftriaxone may be indicated for complicated typhoid fever

15. What % of Typhoid cases
become carriers?
What is the recommended age
for TCV?

16. CHRONIC CARRIAR :2-5 %
RXCIPROFLOX -4 WEEKS
ERRADICATION 80 %
CHOLECYSTECTOMY
IS ALSO RECOMMENDED

17. Generation: Inactivated Whole Cell Vaccine
1st
Generation: Cell Vaccine (Live Oral)
2nd
Generation: Vi Polysaccharide Vaccine
2nd
Generation: Vi Polysaccharide Conjugate Vaccine
3rd
NTS & Paratyphi Conjugate Vaccine
4th
DIFFERENT TYPES OF
TYPHOID VACCINES

18. Proprietary and confidential — do not distribute
Three Typhoid Vaccine
Currently three types of typhoid vaccines are
licensed for use:
i) t Typhoid conjugate vaccine (TCV);
ii) Unconjugated Vi polysaccharide
(ViPS) vaccine;
iii) Live attenuated Ty21a vaccine.
***

19. NEW GENERA TION TYPHOID VA CCINES
New
generation
Typhoid
vaccine
Parenteral
Vi-polysaccharide
(Vi-PS)
Vi-Polysaccharide
Conjugate
vaccines
Conjugated with
Pseudomonas
aeruginosa
exotoxin A (not
available in India)
Conjugated with
Tetanus Toxoid
Oral
(Not available in
India)
Source: Ajay Kalra, Vipin M. Vashishtha. 3.11 TYPHOID VACCINES.
IAP Guidebook on Immunization 2013–14. page no 257-270

20. CONJUGATE VACCINE VERSUS
POLYSACCHARIDE
Sr no Parameters Polysaccharide
Conjugate
polysaccharide
1
T-Cell dependent
immune response
No Yes
2 Immune memory No Yes
3
Effectiveness
< 2 years
Not effective Effective
4 Efficacy Moderate High
5
Post booster
immune response
Hyporesponsivenes
s
Robust
6 IgG class switch Limited Efficient
Source: 1. V Krishna Mohan, Vineeth Varanasi, Anit Singh, Marcela F Pasetti, Myron M Levine, R Venkatesan, and Krishna M Ella. Safety and
immunogenicity of a Vi polysaccharide-Tetanus Toxoid conjugate vaccine in healthy infants, children and adults in typhoid endemic areas: a multi-center,
two-cohort (open-label/double-blind, randomized, controlled), phase III study. Clin Infect Dis. 2015; 61(3):393-402. 2. Klouwen berg and Bont Neonatal
and infantile immune responses to encapsulated bacteria and conjugate vaccines. Clin Dev Immunol.2008; 2008:628963.

21. TYPHOID CONJUGATE VACCINE:
SALIENT FEATURES
• Proven safe and more effective than polysaccharide vaccine1
• Induces high Ab titres in children < 2 yrs of age1
• Produces a T-cell dependent immune response which creates vaccine
immune memory1
• T-cell dependent which induces Vi antibodies that neutralize Vi antigen
unlike T-cell independent plain Vi polysaccharide vaccine1
• May provide long term protection .
• Conjugate will not induce hypo responsiveness to subsequent TyPs2
Source: 1. Ajay Kalra, Vipin M. Vashishtha. 3.11 TYPHOID VACCINES. IAP Guidebook on Immunization 2013–14. page no 257-270.
2. Klouwen berg and Bont Neonatal and infantile immune responses to encapsulated bacteria and conjugate vaccines. Clin Dev
Immunol.2008; 2008:628963.

22. Guidelines on Typhoid Vaccination

23. Typhoid Vaccination (TCV)
Single vaccination
life time efficacy
85%

24. COVISHIELD
vaccination
efficacy
86%

25. Proprietary and confidential — do not distribute
WHO POSITION
TCV is preferred at all ages in view of its
improved immunological properties, use in
younger children and longer duration of
protection.
TCV should be prioritized in countries with high
burden of disease or antimicrobial resistance.

26. Proprietary and confidential — do not distribute
TCV - DOSE
• WHO recommends a 0.5 mL single dose of
TCV in children from 6 months and in adults
up to 45
• In Endemic regions like India… WHO also
encourages routine programmatic
administration of TCV to children at the
same time as other vaccines, at 9 months or
in the second year of life.
ADULTSLIKE YOU & me SHOULD TAKE IT

27. WHO TYPHOID POSITION PAPER - 2018
PRIMARY VACCINATION
• Higher and more sustained levels of immunogenicity
from one dose of TCV
• WHO recommends TCV as a single dose from 6 months
to 45 years in Endemic countries.
World Health Organization . Typhoid vaccines: WHO position paper, March 2018 – Recommendations. Vaccine (2018),

28. Primary vaccination in Children
• WHO encourages routine programmatic administration of
TCV at the same time as other vaccine visits at 9 months of age
or in the second year of life in children .
Catch-up vaccination
• With TCV up to 15 years of age is recommended as burden of
disease and programmatic feasibility are greater in this age
range than in adults
World Health Organization . Typhoid vaccines: WHO position paper, March 2018 – Recommendations. Vaccine (2018),
WHO TYPHOID POSITION PAPER - 2018

29. VACCINE USE IN OUTBREAKS
AND EMERGENCY SETTING
Recommended
REVACCINATION
With TCV not neededUNWRITTEN UMDERSTANDING
WHO TYPHOID POSITION PAPER - 2018

30. Contraindications
the only absolute contraindication to
vaccination is a history of severe local
or systemic reactions following the
previous vaccination.
WHO TYPHOID POSITION PAPER - 2018

31. PREGNANCY
it is safe to used during pregnancy since it is
Bacterial component not a live vaccine.
The Typhoid vaccine available in the USA had
Not Been Studied in pregnant women because
of rarity of problem.
WHO TYPHOID POSITION PAPER - 2018

32. UK GUIDELINES
Typhoid vaccines are given to reduce the risk of a
person catching typhoid.
UK guidelines recommend that pregnant women
should ideally avoid travelling to areas where
typhoid is common.
Women who cannot avoid travelling to these areas
should consider being vaccinated.

33. UK GUIDELINES
When deciding whether to have a typhoid vaccination
during pregnancy it is important to weigh up how
high your risk is of catching typhoid and the known
risks of typhoid infection against the possible but
unconfirmed risks to you or your baby of being
vaccinated in pregnancy, some of which might
depend on how many weeks pregnant you are.
it is not a routine vaccine in pregancy.

34. Proprietary and confidential — do not distribute
WHO POSITION
About Other Vaccines
Countries may also consider the routine use of
ViPS vaccine in those ≥ 2 years, and Ty21a
( oral) vaccine for those > 6 years.

35. USA
• VACCINES GIVEN ARE
ORALLIVE(Ty21a )
attenuated Vivotif
1 cap every other day 4 doses
INJECTABLE Vi capsular polysaccharide ,Typhim Vi 1
dose S/C
1 LIFETIME DOSE
HAVE EFFICACY 70 %
NOT PROTECTIVE FOR PARATYPHI DISEASE

36. RECOMMENDATIONS
Indian Academy of
Pediatrics
(IAP)
• Single dose of any
of Typhoid conjugate
vaccine (TCV 25 mg)
is recommended
from 6 months
onwards and can be
administered with
MMR also.
Centers for Disease
Control and
prevention
(CDC)
• If you are
traveling to a
country where
typhoid is common,
you should consider
being vaccinated
against typhoid
World Health
Organization
(WHO)
• For people
travelling in high-
risk areas where
the disease is
endemic. People
living in such areas,
people in refugee
camps,
microbiologists,
sewage workers and
children should be
the target groups for
vaccination.
Source: http://www.indianpediatrics.net/dec2013/1095.pdf as accessed on 18 Feb 2015, 9:58 pm; https://www.cdc.gov/typhoid-
fever/typhoid-vaccination.html accessed on 17 May 2017 @ 2:30 PM; http://www.who.int/rpc/TFGuideWHO.pdf accessed on 17 May
2017 @ 3:00 PM

37. API RECOMMENDATION
• TCV is preferred at all ages because of its improved
immunological properties and expected longer duration of
protection
• Professional food handlers
• Typhoid patients after full recovery from illness
• It is recommended for travelers or during outbreaks.
• TCV 0.5 ml IM single dose.
• booster dosenot needed.
Source: The Association of Physicians of India. Essential Knowledge Briefings: Adult Immunization in India-Changing the immunization
paradigm. Accessed at: https://www.essentialknowledgebriefings.com/downloads/adult-immunization-in-india-changing-the-
immunization-paradigm/ on 11th Jan 2020 @ 4 PM.

38. TYPHOID INFECTION COST MONEY
EXPLAINS THE NEED FOR ADULT
IMMUNIZATION
• Significant proportion of the cases & deaths due to typhoid
are seen in the adults1
• Typhoid related hospitalization costs alone ranging from
$159 to $636 (in 2016 US$) in India2
• Costs per outpatient case ranged from $16 to $74 in India2
• One attack of typhoid does not provide solid or long lasting
immunity from a future episode of the same illness3
• General recommendation to give typhoid vaccine at least 4
weeks after full recovery from typhoid illness3-4
Source:1. GBD 2016 Causes of Death Collaborators. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic
analysis for the Global Burden of Disease Study 2016. Lancet 2017; 390: 1151–210. 2. Luthra K et al. A Review of the Economic Evidence of Typhoid Fever and
Typhoid Vaccines. Clin Infect Dis. 2019 Mar 7;68(Supplement_2):S83-S95. 3. John TJ. Typhoid vaccination after enteric fever-reply. Indian pediatrics. 1999
Jul;36(7):724-5. 4. Zaki S. Re-infection of typhoid fever and typhoid vaccine (comment on "An imported enteric fever caused by a quinolone-resistant Salmonella
typhi"). Ann Saudi Med. 2011 Mar-Apr;31(2):203-4; author reply 204.

39. HOW TO VACCINATE?
ADULT VACCINATION SCHEDULE
Immunizing dose for adults, children
and infants of age ≥6 months is single
dose of 0.5 mL.
Booster dose: not recommended.

40. HOW TO VACCINATE?
CHILDRENVACCINATION
SCHEDULE
Immunizing dose for children and
infants of age ≥6 months 1 dose of
0.5 mL; booster dose not required
after 3 years

41. FAQS
• How effective is the TCV vaccine?86%
• With a single dose how long would TCV
remain effective? lifetime
• How long after Typhoid disease should TCV
be given?  4 weeks after full recovery.

42. TAKE HOME MESSAGE
• TCV is safe & immunogenic
• Prevents more than 85% of typhoid fever cases
These calculations of vaccine efficacy within
the confines of a stringent challenge model are
likely to be conservative estimates (WHO )
Jin C et al. Lancet. 2017 Sep 28.
TCV Study

43. TAKE HOME MESSAGE
WHAT YOU SHOULD DO
TAKE YOURSELF ,
GIVE TO YOUR STAFF JUST LIKE HEPATITIS
VACCINATION ,
GIVE TO YOUNG GIRLS
Problem of INDIAN sub continent

44. 15P37-053F