Laboratory diagnosis of typhoid - CONTROL OF TYPHOID FEVER

The definitive diagnosis of typhoid fever depends on the isolation of S. typhi from blood, bone marrow and stools. Blood culture is the mainstay of diagnosis of this disease.

Felix-Widal test measures agglutinating antibody levels against O and H antigens. Usually, O antibodies appear on day 6-8 and H antibodies on day 10-12 after the onset of disease. The test is usually performed on an acute serum (at first contact with the patient). The test has only moderate sensitivity and specificity. 

It can be negative in up to 30 per cent of culture - proven cases of typhoid fever. This may be because of prior antibiotic therapy that has blunted the antibody response. On the other hand, S. typhi shares O and H antigens with other salmonella serotypes and has cross- reacting epitopes with other Enterobacteriacae, and this can lead to false-positive results. Such results may also occur in other clinical conditions, e.g. malaria, typhus, bacteraemia caused by other organisms, and cirrhosis.

The recent advances for quick and reliable diagnostic tests for typhoid fever as an alternative to the Widal test include the IDL Tubex® test marketed by a Swedish company, which reportedly can detect IgM09 antibodies from patient within a few minutes. Another rapid serological test, Typhidot, takes three hours to perform. 

It was developed in Malaysia for the detection of specific IgM and IgG antibodies against a 50 kD antigen of S. typhi. A newer version of the test, Typhidot-M®, was recently developed to detect specific IgM antibodies only. The dipstick test, developed in the Netherlands, is based on the binding of S. typhi specific IgM antibodies in samples to S. typhi lipopolysaccharide (LPS) antigen and the staining of bound antibodies by an anti-human IgM antibody conjugated to colloidal dye particles.

The control or elimination of typhoid fever is well within the scope of modern public health. This is an accomplished fact in many developed countries. There are generally three lines of defence against typhoid fever:

The weakest link in the chain of transmission is sanitation which is amenable to control.

The usual methods of control of reservoir are their Identification, isolation, treatment and disinfection.

Since carriers are the ultimate source of typhoid fever, their identification and treatment is one of the most radical ways of controlling typhoid fever. The measures recommended are:

Protection and purification of drinking water supplies, improvement of basic sanitation, and promotion of food hygiene are essential measures to interrupt transmission of typhoid fever. For instance, typhoid fever is never a major problem where there is a clean domestic water supply. Sanitary measures, not followed by health education may produce only temporary results. However, when sanitation is combined with health education, the effects tend to be cumulative, resulting in a steady reduction of typhoid morbidity.

While ultimately, control of typhoid fever must take the form of improved sanitation and domestic and personal hygiene, these are long-term objectives in many developing countries. A complementary approach to prevention is immunization, which is the only specific preventive measure, likely to yield the highest benefit for the money spent Immunization against typhoid does not give 100 per cent protection, but it definitely lowers both the incidence and seriousness of the infection. It can be given at any age upwards of two years. It is recommended to:

The old parenteral killed whole-cell vaccine was effective but produced strong side-effects Two safe and effective vaccines are now licensed and available One is based on defined subunit antigens, the other on whole-cell live attenuated bacteria

This subunit vaccine was first licensed in the United States in 1994 It is composed of purified Vi capsular polysaccharide from the Ty2 S Typhi strain and elicits a T-cell independent IgG response that is not boosted by additional doses. The vaccine is administered subcutaneously or intramuscularly. The target value for each single human dose is about 25µg of the antigen. The vaccine is stable for 6 months at 37°C, and for 2 years at 22°C. The recommended storage temperature is 2-8°C. The Vi vaccine does not elicit adequate immune responses in children aged less than 2 years.

The vaccine is licensed for individuals aged ≥ 2 years. Only 1 dose is required, and the vaccine confers profection 7 days after injection. To maintain protection, revaccination is recommended every 3 years. The Vi polysaccharide vaccine can be co-administered with other vaccines relevant for international travellers, such as yellow fever and hepatitis A, and with vaccines of the routine childhood immunization programmes.

No serious adverse events and a minimum of local side. effects are associated with Vi vaccination. There are no contraindications to the use of this vaccine other than previous severe hypersensitivity reaction to vaccine components. Although the Vi polysaccharide vaccine is safe for HIV-infected individuals, the induction of protective antibodies is directly correlated to the levels of CD4 positive T-cells.

This vaccine, which was first licensed in Europe in 1983 and in the USA in 1989, is an orally administered, live- attenuated Ty2 strain of S. Typhi in which multiple genes, including the genes responsible for the production of Vi, have been mutated chemically. The lyophilized vaccine is available as enteric coated capsules. Protection is markedly influenced by the number of doses and their spacing. There are currently no field trials to document the efficacy of Ty2la vaccine in children aged years. Ty21a requires storage at 2-8°C, it retains potency for approximately 14 days at 25°C.

The capsules are licensed for use in individuals aged ≥ 5 years. The vaccine is administered every other day; on 1, 3, and 5th day, a 3-dose regimen is recommended. With the 3-dose regimen, protective immunity is achieved 7 days after the last dose. The recommendation is to repeat this series every 3 years for people living in endemic areas, and every year for individuals travelling; from non-endemic to endemic countries. The Ty2la vaccine may be given simultaneously with other vaccines, including live vaccines against polio, cholera, and yellow fever, or the measles. mumps and rubella (MMR) combination.

Proguanil and antibacterial drugs should be stopped from 3 days before until 3 days after giving Ty21a, as such drugs may harm live bacterial vaccines. The vaccine is unlikely to be efficacious if administrated at the time of ongoing diarrhoea. It is not known whether this live attenuated vaccine may cause foetal harm when administered to pregnant women. Ty21a can be administered to HIV-positive, asymptomatic individuals as long as the T-cell count (CD4) is >200/mm3.

Ty2la is remarkably well tolerated and has low rates of adverse events. The vaccine is not recommended in congenital or acquired immunodeficiency including treatment with Immuno-suppressive and antimitotic drugs, acute febrile illness and acute intestinal infection.