Vaccines for Enterically Transmitted Diseases in travelers Prof. Eli Schwartz MD,DTMH The Center of Geographic Medicine & Tropical Diseases Sheba Medical Center, Tel-HashomerSackler Faculty of Medicine, Tel-Aviv univ. ISRAEL
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
Typhoid: Global Epidemiology • Greatest burden of disease in ASIA • 13 million cases per year • 400,000 deaths annually • incidence rates as high as 900-1200/105 • rise in cases since 1990s
Annual incidence of Typhoid Fever worldwide Conor BA, Schwartz E.Typhoid and paratyphoid fever in travelers. Lancet Infect Dis. 2005;5:623-8
Typhoid Epidemiology in Developed Countries
Typhoid Epidemiology in Developed Countries Now a travel associated disease in industrialized countries
Incidence of Typhoid Fever (Lt) and % of travelers (Rt)-USA 8 100 90 7 80 6 70 5 60 % travelers 4 50 USA: incidence/100,000 40 3 30 2 20 1 10 0 0 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.
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
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
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 Mediterraneanregion and South America S. paratyphi C Africa Enteric Fever pathogens & Geographic distribution
Rate of infection : S.Typhi vs S.paratyphi Schwarts E. et al, Arch Intern Med 150; 349-351, 1990
Annual cases of S. typhi and S.paratyphi in the UK http://www.hpa.org.uk/infections/topics_az/salmonella/data_typh.htm
Typhoid Prevention “Boil it, Cook it, Peel it or Forget it “ Easy to remember,impossible to do!
Typhoid vaccines Parenteral vaccines (anti Vi): • circulating antibody response Live attenuated oral vaccines(Ty21a): • vigorous secretory IgA response • cell mediated response
Meta-analysis of typhoid vaccine efficacy Engels EA, et al. Typhoid fever vaccines: a meta-analysis of studies on efficacy and toxicity. BMJ 1998; 316: 110–16
Typhoid Vaccine Efficacy 60-70%
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. 349:1390-1391
Typhoid Vaccine Efficacy 60-70% All studies done in endemic areas among local population What it does mean for Travelers ?
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%
Traveler: no pre-existing immunity Try to avoid contaminated food and water More rapid and available access to medical care Differences between traveler and indigenous population • Indigenous population: • Constant boosting • Live in the same condition • more severe clinical course
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; 349-351, 1990
Meltzer E., Sadik C, Schwartz E. Enteric Fever in Israeli Travelers: a Nation-Wide study. J. of Travel Medicine 2005;12:275-81
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?!
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.
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.
Hepatitis A One of the World’s Most Common Infectious Diseases
Geographic Distributionof Hepatitis A Ref: Centers for Disease Control and Prevention MMWR 48(RR-12), 1999
HAV Seroprevalence in Israel 100 94 80 80 60 Prevalence % 55 46 40 20 0 1977 1987 1989 1995 2000 Year
Prevalence of HAV IgG in Israeli Travelers 82 76 68 HAV-IgG Positive 33 24 Age Group (years) Schwartz E. & Raveh D. ; Int J Epidem 27:118-120, 1998
Passive Immunization • Short-term protection – requires frequent renewal • No stimulation of antibody production in recipient • Serum–derived product • Large injection volumes
Active Vaccination • Long-term protection from single course of vaccination • Stimulates antibody production in the recipient • Non serum-derived product • Small injection volumes
HAV Antibody Titres in Persons with Active & Passive Immunization & After HAV Infection Natural infection Vaccinated persons Anti-HAV GMT mIU/ml Passive immunization
Havrix Hepatitis A Vaccine Seroconversion Rates Injections given at months 0 & 1 with a booster at 6 months
Hepatitis A –combined vaccines • Hepatitis A+ Typhoid Fever -Hepatirix – GlaxoSmithKline, Viatim-Sanofi Pasteur • Hepatitis A +B - Twinrix – GlaxoSmithKline
Be careful! Thank you !