•Typhoid fever (also known as enteric fever) is a bacterial infection occurring in the intestinal tract and occasionally, in the bloodstream.

•It is caused by the bacterium Salmonella typhi -a unique human strain of salmonella. It is a rod shaped, gram negative bacterial pathogen, being motile with the aid of flagellum.

•In nature, S. typhi is often found on open sewage and in the gut of animals.

•Typhoid fever cases are most common in areas within Asia, Africa and Latin America, therefore a greater risk lies in travellers to those regions being affected by the disease.

The bacterium Salmonella typhi

How is it spread?•Transmission of the bacterium often occurs when food or water is contaminated by carriers of the disease and is then digested by others.

•Typhoid can also be transmitted by flies landing on open sewage, picking up the bacteria, and then contaminating food, which is again eaten by humans. Spreading in this way is known as indirect host-host transmission.

Flies carry disease by picking up infectious agents on their feet

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Creating Cultures

Blood Cultures: used to determine the presence of microorganisms such as bacteria in the blood.

•A blood sample from the individual is placed in a special laboratory preparation and incubated for up to seven days.

• It is important that the conditions within the environment are controlled to avoid contamination.

•If organisms are observed in the sample, it may be cultured further, and a Gram stain may also be done in order to determine the particular organism, so that antibiotic courses can be started for the affected individual.

•Approximately 80% show a positive result, usually in the first week of infection.

Stool/ Faecal Culture: used in a laboratory as a test to isolate and identify pathogenic organisms present, which may cause gastrointestinal symptoms and disease-in this case the pathogen S. typhi.

•Growth of microorganisms is encouraged by placing a sample in a culture medium.

•At regular intervals, the culture is observed for growth. Growth enables the organism present to be identified. Further tests may then be performed on the organism.

•Stool cultures show a positive result at later stages of the infection, usually in 30-60% of cases.

•Bone marrow and urine cultures may also be carried out.

Identifying salmonella typhi

As isolating a pathogen is not always likely in identifying the possiblity of infectious disease, an antibody titer is performed. ‘Titer’ refers to quantity. Generally, the method involves a serial dilution of serum from the individual concerned. The highest dilution at which the antigen-antibody reaction occurs is the point at which any sign of infection is determined. One way of measuring antibody titer is:

•Agglutination which refers to the resulting mixture formed when a particular antigen and antibody specific for that antigen is mixed. It is observed as a visible clumping of the antigen..

ELISA (enzyme-linked immunosorbent assay)

This is a more effective means of identifying pathogens. It uses antibodies to which enzymes are attached to, leading to both the catalytic activity of the enzyme and the specificity of the antibody to remain unchanged. There are two methods:

•Direct ELISA- detects antigens

•Indirect ELISA- detects antibodies

For human serum, either of the above methods are used, depending on which is being detected.

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•After ingestion, S.typhi travel down the digestive tract where they are taken in by phagocytes. These are important white blood cells within the immune system, engulfing and destroying ‘foreign’ bacteria and viruses invading the body.

•However, S. typhi are able to resist this process and rapidly multiply inside the phagocyte. The time period taken to do this is the 10-14 day incubation period of typhoid fever.

•The cell then bursts, causing the huge numbers of bacteria to spill into the bloodstream. It is then that symptoms of typhoid fever begin to show.

• The bacteria then begin invading certain tissues of the intestine. This eventually leads to perforation of intestine, which then in turn results in peritonitis -leakage of the intestinal contents-and can cause death.

•Other effects of typhoid fever include liver and spleen enlargement. Meningitis and brain infections may occur in the most sever cases and may even lead to coma.

Symptoms

•High fever

•Diarrhoea

•Headaches

•Constipation

•Possible outbreak of ‘rose spots’-a rash of rose coloured spots, characteristic of typhoid fever.

•Slow heart rate (bradycardia)

•Muscle pain (myalgia)

•Extreme symptoms include intestinal perforation, spleen and liver enlargement.

Example of ‘rose spots’ on an affected individual

Image showing perforation of the small intestine.

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•The most common method of treating typhoid is through a course of Penicillin or Quinolone based antibiotics, ampicillin and ciprofloxacin respectively. The antibiotic chloramphenicol is also used.

•Intravenous fluids and electrolyte therapy may also be given to replace fluids and salts lost due to diarrhoea. This is especially important for children suffering with typhoid fever.

•Immediate treatment with antibiotics means the fatality rate is reduced to about 1%.

•Research shows that Cefpodoxime-’an oral third generation cephalosporin’ seems an effective molecule in its activity against salmonella species, within paediatric typhoid fever. However limitation lies in the lack of clinical trials carried out.

• Experiment with a live, attenuated vaccine for typhoid is also underway and shows the possibility of success.

Map showing the areas affected by typhoid

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As the spreading of typhoid fever occurs mainly through poor sanitation, public education campaigns promote the washing of hands after using the toilet as well as prior to handling food. These are essential ways of controlling the transmission of salmonella typhi and therefore preventing the risk of typhoid fever.

•Adequate water treatment, waste disposal and the prevention of food supply contamination is necessary.. This means that carriers of the disease must not work as food handlers.

•The filtration and chlorination of water as a method of purification has also proved very successful in reducing the risk of typhoid fever.

Spreading of the disease can also be prevented by isolating individuals who have active diarrhoea, but are unable to control their bowels i.e. infants, certain handicapped people. This is due to the fact that the bacterium can be passed in the faeces of those infected.

•Some people, however, may become an asymptomatic carrier of typhoid fever, not affected by the symptoms themselves but having the ability to infect others.

•It is thought that roughly 5% who initially suffer from typhoid fever, then carry on the disease after recovery.

Immunisation is encouraged for those travelling to areas where typhoid fever is endemic, such as Asia, Africa and Latin America. Currently, two vaccines are available:

•Typhim Vi: is a killed-bacteria vaccination based on the purified Vi polysaccharide of salmonella typhi.

•Vivotif/Ty21a: is a live bacteria vaccination, administrated orally.

Although both vaccines provide protection against typhoid fever, neither is 100% effective, nor do they protect against unrelated typhus.

The typhim Vi vaccine

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Books

Brock-Biology of Microorganisms

11th Edition

Authors: M.T.Madigan, J.M Martinko

Websites

www.health line.com/gale content/typhoid fever

http://www.who.int/vaccines/en/typhoid.shtml

http://www.who.int/infectious-disease-report/2000/graphs/4_mdr-salmonella.htm

http://www.denniskunkel.com/DK/DK/Bacteria/96430B.html

http://www.cdc.gov/NCIDOD/DBMD/diseaseinfo/typhoidfever_g.htm

http://en.wikipedia.org/wiki/Typhoid_fever

http://www.lenntech.com/Waterborne-diseases/typhoid.htm

http://health.utah.gov/epi/fact_sheets/typhoid.html

http://www.emedicine.com/MED/topic2331.htm

Articles-Medline

Title: Problem pathogens: extra-intestinal complications of Salmonella enterica serotype Typhi infection.

Authors: D.B.Huang, H.L Duport

NLM Journal Code: 101130150

Title: Cefpodoxime - utility in respiratory tract infections and typhoid fever.

Authors: A.Aggarwal, S.Rath

NLM Journal Code: gkt, 0417442

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