Typhoid is caused by Salmonella enterica subspecies enterica serovar Typhi (previously Salmonella typhi). Humans are the only reservoir of S. Typhi. Transmission is via the ingestion of faecally contaminated food or water. In Malaysia, typhoid is among the food and water borne diseases besides cholera, food poisoning, hepatitis A and dysentery which are notifiable under the Prevention and Control of Infectious Diseases Act 342.
A classical case of typhoid fever presents with fever, headache and constipation (typically diarrhoea in young children). Clinical findings include abdominal tenderness, relative bradycardia and splenomegaly. Complications occur in 10% of cases which may result in intestinal perforation, gastrointestinal haemorrhage and encephalopathy. Up to 5% of patients with typhoid fever may become chronic carriers and may continue to shed (through the patients faeces) the organisms for more than 1 year. Carriers serve as reservoirs in endemic areas and are of considerable public health importance, particularly if they work in the food industry.
Typhoid is endemic in Malaysia with an average incidence rate of 0.76 per 100 000 population reported annually in recent years (2014-2019). The incidence rate was 0.53 per 100,000 population in 2018.
Typhoid is also regarded as a travel-related disease with a considerably higher risk following travel to the Indian subcontinent, most Southeast Asian countries and several South Pacific nations.
The importance of vaccination for typhoid is heightened by increasing resistance of S. Typhi to antimicrobial agents, including fluoroquinolones, in many parts of the world.
There are 2 types of typhoid vaccines which are available in oral or parenteral formulation.
The oral vaccine contains the attenuated non-pathogenic S. Typhi strain Ty21a which is derived by chemical attenuation of a wild-type strain. The vaccine lacks the Vi capsular polysaccharide antigen; an important virulence factor of S. Typhi.
The parenteral vaccine contains purified Vi capsular polysaccharide of S. Typhi (Ty 2 strain). The purified polysaccharide capsule is diluted in isotonic buffer solution which contains phenol as preservative.
Vaccines Available in Malaysia
1. Typhim Vi® (Purified Vi capsular polysaccharide, single or 20 doses)
Sanofi Aventis (M) Sdn Bhd/Sanofi Pasteur, France
Propharm (M) Sdn Bhd/PaxVax Berna, Switzerland
3. Typherix® (Purified Vi capsular polysaccharide)
GlaxoSmithKline Pharmaceutical Sdn Bhd/GlaxoSmithKline Biologicals, Belgium
Mode of Administration
Oral live attenuated vaccine
It is available in a pack of 3 capsules. The vaccine schedule is as follow: 1 capsule on each of days 1, 3 and 5 to be taken 1 hour before meals with cold or lukewarm water (not more than 37oC). The capsule must be swallowed whole and not chewed.
Parenteral Vi polysaccharide vaccine
The monovalent typhoid vaccine is given as a single dose of 0.5 ml via IM injection.
Typhoid vaccines lose effectiveness over time. The injectable vaccine requires a booster every 2 years and the oral vaccine requires a booster every 5 years.
Co-administration with Other Vaccines
- Oral typhoid vaccine can be administered simultaneously as any of the live parenteral vaccines and immunoglobulins. It is recommended that the last dose of vaccination be given at least 3 days before starting antibiotics or anti-malarial prophylaxis as these drugs may interfere with the protective effect of the live attenuated vaccine.
- Parenteral Vi polysaccharide typhoid vaccine can be given with other vaccines indicated for travel.
Contraindications and Adverse Effects
The only absolute contraindication to typhoid vaccine is anaphylaxis reaction after a previous dose to any typhoid vaccine or to any component of the vaccine. Both types of vaccines are associated with very few adverse reactions.
Oral live attenuated vaccine should not be administered to pregnant women, immunocompromised persons and persons taking antibiotics. Adverse reactions include abdominal discomfort, diarrhoea, nausea and vomiting.
Parenteral Vi polysaccharide vaccine may cause adverse effects such as local reactions at the injection site consisting pain, redness and swelling. Fever and headache may be present.
To date, the reported adverse events for typhoid vaccine received by the National Adverse Drug Reactions Monitoring Centre (NPRA) are erythema, fever and diarrhoea.
Target Groups in Malaysia
Food handlers and vendors.
Travelers to areas in which there is a recognised risk of exposure to S. Typhi.
The parenteral vaccine should be given at least 2 weeks before travel
For the oral vaccine, all doses should be completed at least 1 week before travel
Risk is greatest for travelers to developing countries where food hygiene may be suboptimal and drinking water may not be adequately treated. Travelers should be cautioned that typhoid vaccination is not a substitute for careful selection of food and drink as the efficacy is only about 60-70%.
Persons with close contact (household contact) to a documented S. Typhi carrier.
Implications for Healthcare Workers (HCWs)
- Typhoid vaccines should be employed as part of comprehensive control strategies in areas where the disease is endemic. Working in a health care setting is not indicated as a factor for increased risk. There is currently no recommendation regarding HCWs
Evidence for Effectiveness
- Clinical trials with different formulations of the oral vaccine Ty21a strain in a variety of schedules, have been undertaken in countries (Egypt, Chile and Indonesia) where typhoid is endemic. These have documented varying degrees of protection against the disease. Parenteral Vi polysaccharide vaccines have also been used in clinical trials in endemic regions (Nepal, South Africa, China), indicating moderate protection against typhoid fever.
- In controlled trials conducted among schoolchildren in Chile, 3 doses of the Ty21a vaccine in enteric-coated capsules administered on alternate days reduced laboratory-confirmed infection by 66% over a period of 5 years.
- A meta-analysis comprising 17 studies and nearly 2,000,000 people showed that for the whole cell vaccines, single dose regimens provide significant protection for the first 2 years. Two dose regimens provided significant protection for 5 years. For the Ty21a vaccine, both the 2-and 3-dose regimens provided statistically significant protection for 2 years. The 3-dose regimen provided protection in the 3rd and 4th years, but protection was not statistically significant in the 5th year. The Vi polysaccharide vaccine provided protection for 2 years, but the protection in the 3rd year was not significant.
- Bhan, M.K., Bahl, R., Bhatnagar, S. (2005). Typhoid and paratyphoid fever. The Lancet, 366, 749-62
- Centers for Disease Control and Prevention (CDC). (2011). Recommendation of the Advisory Committee on Immunisation Practices (ACIP). Immunisation of Health-Care Personnel. MMWR, 60(7). https://www.cdc.gov/mmwr/pdf/rr/rr6007.pdf
- Centers for Disease Control and Prevention (CDC.) (2015). Advisory Committee on Immunization Practices. Updated Recommendations for the Use of Typhoid Vaccine. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6411a4.htm
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