1. Vaccines for Enterically Transmitted Diseases
in travelers
Prof. Eli Schwartz MD,DTMH The Center of Geographic Medicine & Tropical Diseases Sheba Medical Center, Tel-Hashomer Sackler Faculty of Medicine, Tel-Aviv univ. ISRAEL

2. Typhoid: Global Epidemiology

3. Typhoid: Global Epidemiology
33 Million cases annually
600,000 deaths
Incidence rates
low: <1/105 population in developed countries
high: >800/105 population in endemic areas

4. Typhoid: Global Epidemiology
Greatest burden of disease in ASIA
13 million cases per year
400,000 deaths annually
incidence rates as high as /105
rise in cases since 1990s

5. Annual incidence of Typhoid Fever
worldwide
Conor BA, Schwartz E.Typhoid and paratyphoid fever in travelers. Lancet Infect Dis. 2005;5:623-8

6. Typhoid Epidemiology
in Developed Countries

7. in Developed Countries
Typhoid Epidemiology
in Developed Countries
Now a travel associated disease
in industrialized countries

8. Incidence of Typhoid Fever (Lt) and % of travelers (Rt)-USA8
100 90 7 80 6 70 5 60 4 50
% travelers
USA: incidence/100,000 40 3 30 2 20 1 10
1940
1945
1950
1955
1960
1965
1970
1975
1980
1985
1990
1995
2000
USA: incidence/100,000
% travelers
Connor BA, Schwartz E. Typhoid and paratyphoid fever in travelers.Lancet Infect Dis. 2005;5:623-8.

9. Risk Factors Travel to rural areas with poor sanitation
Not following food and water precautions
Not receiving pre-travel consultation
Length of stay
VFR’s

10. The pathogens Enteric fever, the more inclusive term, is caused by
Salmonella enterica serotypes S. typhi and S. paratyphi.
S. Typhi
S. paratyphi A
S. paratyphi B
S. paratyphi C

11. Enteric Fever pathogens Geographic distribution
&
Geographic distribution
The bacteria
Geographic distribution
S. typhi
Developing countries, manily the Indian subcontinent and South-East Asia
S. paratyphi A
Indian subcontinent
S. paratyphi B
Indonesia, Malaysia, the Mediterranean region and South America
S. paratyphi C
Africa

12. Local population (Nepal)
Rate of infection : S.Typhi vs S.paratyphi
S.typhi
S.paratyphi
Local population (Nepal)
80%
20%
Unvaccinated
67%
33%
Vaccinated
32%
68%
Schwarts E. et al, Arch Intern Med 150; , 1990

13. Annual cases of S. typhi and S.paratyphi in the UK

14. Enteric Fever episodes in Asian Countries
China
India
Pakistan
Indonesia
Country
Hechi city
Calcutta
Karachi
Jakarta
Site
2001-2
2003-4
2002-3
Period
5-60
All ages
2-16
Age group (Y)
64%
24%
15%
14%
% S.para A

15. “Boil it, Cook it, Peel it or Forget it “
Typhoid Prevention
“Boil it, Cook it, Peel it or Forget it “
Easy to remember, impossible to do!

16. Typhoid vaccine

17. Typhoid vaccines Parenteral vaccines (anti Vi):
circulating antibody response
Live attenuated oral vaccines(Ty21a):
vigorous secretory IgA response
cell mediated response

18. Ty21a
Vi -vaccine
Mucosal
Humoral
Mode of action
Live atenuated
Killed
Type
Avirulent
(lack Vi)
Anti Vi (S.typhi)
Target
3-4 doses
1 dose
N. of doses
Contraindication
Ab, antimalaria
Hep A
Combination
3-4 y
2-3 Y.
Booster
.> 6 y.
>2 y
Age

19. Meta-analysis of typhoid vaccine efficacy
Year 5 4 3 2 1
Efficay:
% (95% CI)
No data
50(-11-78)
52(4-76)
67 (44-81) Vi
(1 dose)
47(-24-78)
78 (35-93)
60(35-76)
60 (44-71)
50 (18-69)
Ty21a
(3 doses)
67(43-80)
73 (42-87)
74(50-87)
72 (56-82)
74 (62-82)
Whole cell (2 doses)
Engels EA, et al. Typhoid fever vaccines: a meta-analysis of studies on efficacy and toxicity. BMJ 1998; 316: 110–16

20. Summary of Toxicity study on Typhoid Vaccines
Whole cell
(TAB)
Ty21a Vi
% A.E
15.7 ( )
2 ( )
1.1 ( )
Fever
20.0 ( ) -
3.7 ( )
Swelling
2.1 ( )
Vomiting
5.1 ( )
Diarrhea
10.0 (6-16.2)
Missed work/school

21. Typhoid Vaccine
Efficacy 60-70%

22. Vi-Conjucated Vaccine (rEPA) [nontoxic recombinant Pseudomonas aeruginosa exotoxin A]
Highly immunogenic
Cumulative efficacy ~ 90%
Long term immunity
Probably immungenic in Infants <2 y.
Lanh, M. N. et al ; N. Engl. J. Med. 349:

23. Typhoid Vaccine Efficacy 60-70%
All studies done in endemic areas among local population
What it does mean for Travelers ?

24. Typhoid Vaccine Immunity : relative and can be overcome
immunity can be overcome if large infecting dose is ingested
protective effect of prior clinical infection only 28%

25. Differences between traveler and indigenous population
no pre-existing immunity
Try to avoid contaminated food and water
More rapid and available access to medical care
Indigenous population:
Constant boosting
Live in the same condition
more severe clinical course

26. Typhoid: risk to the traveler
CIWEC Clinic, Kathmandu
Risk of acquiring enteric fever:
vaccinated : 12/105
unvaccinated: 217/105
Schwartz E. et al, Arch Intern Med 150; , 1990

27. Meltzer E. , Sadik C, Schwartz E
Meltzer E., Sadik C, Schwartz E. Enteric Fever in Israeli Travelers: a Nation-Wide study. J. of Travel Medicine 2005;12:275-81

28. Typhoid Vaccine: conclusions
Vi vaccine- better protection for S.typhi
Ty21a vaccine-better protection for S.paratyphi A
Their mode of action is different, mucosal vs. humoral immunity
Should we recommend a sequential immunization: Vi vaccines and Ty21a?!

29. Conclusions Typhoid vaccine is an important tool to protect travelers
A more effective Typhoid vaccine is needed
It should includes a Paratyphi A coverage as well.

30. Typhoid Vaccine: conclusions
Typhoid fever remains a major health problem for travelers. All travelers to endemic areas are at potential risk.
Increasing antimicrobial resistance has made preventive strategies even more essential.
Typhoid fever vaccination may be offered to travelers to destinations where the risk of typhoid fever is high, and/or in locations where antibiotic-resistant strains of S. Typhi are prevalent.
Vi and the Ty21a vaccines provide appreciable levels of protection and have a good record of safety.

31. One of the World’s Most Common Infectious Diseases
Hepatitis A
One of the World’s Most Common Infectious Diseases

32. Geographic Distribution of Hepatitis A
Ref: Centers for Disease Control and Prevention MMWR 48(RR-12), 1999

33. Prevalence Changes with Improvement in Hygiene

34. Age-Specific Prevalence (%) of Anti-HAV in the Athens Area

35. HAV Seroprevalence in Israel
100 94 80 80 60
Prevalence % 55 46 40 20
1977
1987
1989
1995
2000
Year

36. Prevalence of HAV IgG in Israeli Travelers82 76 68
HAV-IgG Positive 33 24
Age Group (years)
Schwartz E. & Raveh D. ; Int J Epidem 27: , 1998

37. Hepatitis A: Clinical Characteristics of Patients by Age Group
40+ yrs
15-39 yrs
<1-14 yrs
Clinical Characteristics
70.3%
86.8%
81.7%
Jaundice
41.6%
23.2%
17.1%
Hospitalized for Hepatitis
2.1%
0.3%
0.1%
Death as a result of Hepatitis

38. Passive Immunization Short-term protection – requires frequent renewal
No stimulation of antibody production in recipient
Serum–derived product
Large injection volumes

39. Active Vaccination
Long-term protection from single course of vaccination
Stimulates antibody production in the recipient
Non serum-derived product
Small injection volumes

40. HAV Antibody Titres in Persons with Active & Passive Immunization & After HAV Infection
Natural
infection
Vaccinated persons
Anti-HAV GMT mIU/ml
Passive immunization

41. Havrix Hepatitis A Vaccine Seroconversion Rates
Injections given at months 0 & 1 with a booster at 6 months
Blood Sample Taken
Month 7 6 2 1
100
99.9
95.6
% Seroconversion

42. Hepatitis A –combined vaccines
Hepatitis A+ Typhoid Fever
-Hepatirix – GlaxoSmithKline, Viatim-Sanofi Pasteur
Hepatitis A +B
- Twinrix – GlaxoSmithKline

43. Be careful!
Thank you !