Recommendations for UseThe public health burden of enteric fever in India is huge. Improvements in hygiene and sanitation are still a distant dream. The IAPCOI therefore recommends the inclusion of typhoid vaccines in the national immunization schedule. For office practice, the IAPCOI recommends the administration of the currently available Vi polysaccharide vaccine 0.5 ml IM every three years beginning the age of 2 years till age of 18 years in all children/adolescents who can afford to use the vaccine (Category 2). A child with history of suspected/ confirmed enteric fever may be vaccinated 4 weeks after recovery if he/she has not received the vaccine in the past 3 years. The committee awaits further data on the conjugate typhoid vaccines before recommending them for routine use. It also stresses the need for development of vaccines against paratyphoid fever for both better individual protection and reduction of enteric fever burden. |
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Enteric fever (typhoid and paratyphoid) is a major public health problem in India. Population based studies from urban population in India suggest that incidence of typhoid fever is 2730 per 100,000 populations per year in 0-4 year old children, 1170 per 100,000 per year in 5-19 year age group and 110 per 100,000 per year in 20-40 year age group. The incidence of paratyphoid fever is increasing in India, and may account for 20-40% cases of enteric fever. High prevalence of antimicrobial resistance particularly to quinolones has made enteric fever a difficult disease to treat. All these factors have made vaccines against typhoid and paratyphoid fever of immense need in our country.
Several vaccines have been available against typhoid/ paratyphoid fever.
These were the earliest vaccines available. These vaccines were best suited for developing countries as they were efficacious in children as young as 6 months, inexpensive, provided protection against both typhoid and paratyphoid and had efficacy at least as good as the currently available vaccines. However increased reactogenicity led to discontinuation of use of these vaccines and they are no longer available. For further details please refer to earlier editions of the book.
Salmonella typhi Ty21a is a live attenuated strain with a mutation in gal E gene and lacks the enzyme UDP-gal 4 epimerase. It is genetically stable and is not known to revert to virulence. It provides protection by inducing local gut immunity, but there is no biological marker of immunity for this vaccine. Since the bacteria are acid labile, the vaccine is supplied in an enteric coated formulation as capsules or liquid formulation. Efficacy drops over time and the cumulative efficacy at three years of 3 doses of the capsule formulation against culture confirmed typhoid fever has been reported as 48% in a Cochrane metanalysis. The liquid formulation has superior efficacy but is not available commercially.
The vaccine should be stored at 2 to 8° C. The commercially available capsular form can only be given to children five years of age and above as the capsules have to be swallowed intact. Three doses on alternate days on an empty stomach with cool liquid are recommended. The vaccine should not be given during diarrhoea and antimicrobials active against typhoid bacillus should not be used 3 days before and 3 days after oral typhoid vaccine administration as these may interfere with the vaccine “take”.
The vaccine may be administered with all other childhood vaccines including live vaccines. Protection begins within a week after completion of the course. Revaccination is recommended every 3-7 years. No adverse effects were noted in clinical trials. The vaccine should be avoided during pregnancy and in the immunocompromised (may be given in HIV infected with CD4 count more than 200 cells/ìl). This vaccine has long been withdrawn from the Indian market.
The vaccine contains highly purified antigenic fraction of Vicapsular polysaccharide antigen of S typhi which is a virulence factor of the bacteria. Each dose contains 25-30 ìg of purified polysaccharide in 0.5 ml of phenolic isotonic buffer for intramuscular or subcutaneous use. The vaccine should be stored at 2 to 8o C and should not be frozen. Since it is a pure polysaccharide vaccine, it is not immunogenic in children below 2 years of age and has no immune memory. The biological marker is anti Vi antibodies and 1 ìg/ml is proposed as the serologic correlate of protection. The vaccine does not interfere with the interpretation of the WIDAL test.
Efficacy drops over time and the cumulative efficacy at 3 years against culture confirmed typhoid fever is reported as 55%. It is recommended for use as a single dose in children aged 2 years and above and can safely be given with all other childhood vaccines.
Revaccination is recommended every 3 years. The adverse effects are mild and include pain and swelling at injection site. The vaccine is contraindicated only in those with previous history of hypersensitivity to the vaccine and can be safely given in the immunocompromised including HIV infected.
Conjugation of the Vi antigen with a protein carrier is desirable as it would induce a T-cell dependent immune response including immunogenicity in children aged below 2 years and immune memory. Conjugation of Vi antigen with non toxic recombinant Pseudomonas aeruginosa exotoxin A (rEPA) has been evaluated in safety, immunogenicity and efficacy trials in Vietnam. Two doses administered 6 weeks apart showed immunogenicity superior to Vi polysaccharide vaccine and a cumulative 3 year efficacy of 89% in 2-5 year old children.
Another conjugate vaccine which has recently been licensed in India has Vi antigen conjugated with tetanus toxoid (Peda typh). In a multicentric study from India in 169 subjects aged 12 weeks and more, at least four-fold rise in antibody titer was seen in all subjects following a single dose of the vaccine. The vaccine was well tolerated with no major local or systemic side effects. No data on duration of immunity and efficacy is available. The manufacturer recommends 2 doses of 0.5 ml intramuscularly at an interval of 4-8 weeks, followed by a booster every 10 years. In children aged less than 2 years an extra booster 2-2½ years after the first dose is recommended.
Since the immunogenicity trial assessed response to only single
dose and did not assess duration of immunity the dosing
schedule seems arbitrary. The extrapolation of efficacy of the
vaccine from the Vietnamese trial is invalid due to fundamental
differences between the two vaccines, age groups and dosing
schedule.