Infectious Diseases

Updated 19 May 2015

Typhoid fever

Typhoid fever is an acute severe illness caused by the bacterium Salmonella typhi.

  • Typhoid fever is an acute severe illness caused by the bacterium Salmonella typhi.
  • It is acquired by swallowing the organism in contaminated food or water.
  • It only affects humans.
  • Typical symptoms are fever, headache, abdominal pain, rash, diarrhoea and an enlarged spleen.
  • It can be cured with appropriate antibiotics.

What is typhoid fever?
Typhoid fever is an acute severe illness caused by the bacterium Salmonella typhi. The infection may affect many organ systems in the body, and so there are a variety of symptoms. Typhoid fever was described as long ago as ancient Greek times, and has claimed many lives over the centuries. In the Anglo-Boer war, the British lost more troops from typhoid fever than from war wounds!

How common is typhoid fever?
It is estimated that at least 12 to 13 million cases occur per year worldwide. In South Africa the disease is endemic, meaning that it is constantly present, and occurs at a low level of frequency, although the potential for outbreaks does exist.

How do you get typhoid fever?
S. typhi is excreted in the faeces of infected people as well as by some people who are carriers – they harbour the organism in their gastrointestinal tract without being obviously ill.

If you come into contact with contaminated food or water, and ingest enough of these organisms, you may get typhoid fever. Your stomach acid can kill the organisms, but if you ingest enough bacteria, some will make it past the stomach. So, the more bacteria you ingest, the greater your chance of becoming ill.

Typhoid is more likely to occur in situations where personal hygiene or waste disposal facilities are inadequate, or there is overcrowding. Faecal contamination of water supplies or food is more likely to occur under these circumstances. The disease therefore tends to occur in places such as refugee camps, in wartime conditions, and in conditions of extreme poverty.

What happens once you’ve become infected?
If the organisms survive past the stomach, they move into the small bowel and invade through the wall of the small intestine. They move into and multiply in the lymph nodes around the bowel. In fact, they actually multiply inside some of the cells in the lymph node, and their ability to survive inside these cells is an important factor contributing to their ability to cause infection. After multiplication, they pass from the nodes into the bloodstream, from where they are able to invade a variety of organs in the body. This is the stage when you start having symptoms of typhoid fever.

The incubation period of typhoid (the time between becoming infected and developing symptoms) is about one to three weeks but can be as long as 60 days. The symptoms are variable, but commonly include fever, drowsiness or confusion, headache, nausea, muscle aches and abdominal pain. There may be a rash on the abdomen – rose-coloured spots on the skin (this only occurs in about 20 - 30% of patients). Diarrhoea occasionally occurs, particularly in children and HIV-infected people. In adults, constipation may in fact sometimes occur instead. If diarrhoea does occur, it is usually slightly later in the course of the illness. Other symptoms and signs include a relatively slow pulse (despite the fever), an enlarged spleen and possibly a dry cough.

If left untreated, about 12 – 20% of people with typhoid will die. However, with appropriate antibiotics (see later), the mortality rate is less than 1%. In untreated cases, the infection usually lasts two to four weeks. About 10% of survivors will relapse (i.e. have another attack of typhoid), and about 3% will become carriers. In this situation, the organisms are excreted intermittently in the faeces for months or years. The organisms are believed to take up residence in the gallbladder, and many carriers have been found to have disease of this organ, such as gallstones or chronic cholecystitis (inflammation of the gallbladder). In some instances, people who are found to be carriers have never had obvious typhoid fever, and were thus infected asymptomatically.

Typhoid Mary is probably the most famous carrier of typhoid. She contracted typhoid in 1901, and subsequently became a carrier. In 1914 she was employed as a cook at a hospital in New York, where she is believed to have been responsible for a number of cases of typhoid among the staff.

What are the possible complications of typhoid?
Typhoid fever can give rise to various complications, such as:

  • Perforation of the bowel:
    Typhoid can causes ulcers in the intestinal wall, which may perforate, allowing the bowel contents to contaminate the abdominal cavity. This gives rise to peritonitis, which is a potentially life-threatening infection.
  • Bleeding from the bowel:
    Just as the ulcers can perforate, they may also erode into a blood vessel in the bowel wall, causing bleeding into the bowel. This is also a very serious complication of typhoid.
  • Osteitis:
    Infection of bones can occur with S. typhi, and it typically causes an infection of the vertebrae (spine).
  • Cholecystitis:
    When the organisms spread throughout the body, one of the organs they infect is the gallbladder. Sometimes they don’t cause infection here, but are able to survive in the gallbladder, and are shed periodically into the bowel and thus into the faeces. This gives rise to the carrier state (see earlier).
  • Hepatitis:
    The organism can cause inflammation of the liver, with abnormalities of the liver’s normal function. This is thought to be due to toxins released by the organism, rather than by the organism itself.

Other complications include meningitis (inflammation of the lining of the brain), endocarditis (infection of the heart valves) and pneumonia.

How is typhoid fever diagnosed?
Some of the clinical features – fever, headache, a relatively slow pulse, large spleen, rose coloured rash, abdominal pain – can be suggestive of typhoid. Unfortunately, none of these are diagnostic of typhoid i.e. many other conditions can also result in some of these symptoms or signs. Some laboratory investigations may help with diagnosis:

  • Blood count:
    People with typhoid fever often have a lower than normal white blood cell count. This is unusual, since the white blood cell count often goes up in infections. There may also be evidence of anaemia (low concentration of haemoglobin, the protein in red blood cells that carries oxygen).
  • Liver functions:
    As mentioned previously, there are sometimes abnormalities of certain liver functions that may be detectable in the laboratory.
  • Serological tests:
    Your body makes antibodies to certain proteins found on the surface of the S. typhi bacterium. These antibodies can be looked for in the laboratory using a test called the Widal test. Unfortunately, this test is not always positive in patients who have typhoid (up to 30% of patients who have typhoid have a negative Widal). It can also be positive in patients who do not have typhoid fever. This test is thus not always very helpful, but it may provide an additional clue towards making the diagnosis.
  • Culture of the organism:
    This is the best way to make the diagnosis. Samples of blood, bone marrow, urine and stool should be sent for culture if typhoid is suspected. If the organism is grown and identified in someone with the appropriate symptoms, then they have typhoid fever.
    • Blood culture is positive in about 80% of cases (usually in the first week).
    • Bone marrow culture is positive in up to 95% of cases but bone marrow cultures are not done as frequently as blood cultures since they are more difficult to take.
    • Stool culture can be positive in 30 – 60% of patients (often later in the infection). Stool culture will also be positive in carriers, so a positive stool culture doesn't always mean the person has typhoid fever.
    • Urine culture is positive in only 5 – 10% of cases.

How is typhoid fever treated?
Antibiotics form the mainstay of treatment. A variety of antibiotics are active against S. typhi. The ones most commonly used are amoxicillin, chloramphenicol, cotrimoxazole, ceftriaxone and ciprofloxacin. The first three are all very effective and relatively cheap, which makes them attractive for use in developing countries.

Unfortunately, resistance to these antibiotics is occurring increasingly in S. typhi. Chloramphenicol has the added disadvantage of being associated with some side-effects (such as bone marrow failure) and does not decrease the chance of someone becoming a carrier. Both amoxicillin and cotrimoxazole reduce the risk of the carrier state, and amoxicillin in particular has very few side-effects. These antibiotics are usually given for 14 days.

If the organism is resistant to the above three agents (or if there is a concern about side-effects), ceftriaxone and ciprofloxacin are also very effective, but are more expensive. However, many medical experts now consider ciprofloxacin to be the best drug to treat typhoid. Treatment with ciprofloxacin clears the organism from the bowel more rapidly than amoxicillin or cotrimoxazole, is convenient to take (twice a day), and in uncomplicated cases can be given for a shorter time than amoxicillin or cotrimoxazole (seven days compared to 14 days).

If there are complications such as bowel perforation or bleeding from the bowel, surgery may be needed. In cases of osteitis, antibiotics may need to be given for up to six weeks.

Treatment of carriers:
If someone is shown to be a carrier (defined as shedding the organism in stool one year after infection), they need to be treated. If there are abnormalities of the gallbladder, removing the gallbladder often eliminates the carrier state (in conjunction with antibiotics for about three weeks). If the gallbladder is normal, then antibiotics alone can be tried for four to six weeks. However, sometimes eliminating carriage can be very difficult. If someone is a carrier, they should not be allowed to work in food handling or processing jobs until elimination of carriage has been confirmed.

Can typhoid be prevented?
The best way to prevent typhoid fever is to observe standard hygienic practices when preparing food. If you live in the city this is usually not a problem, but for those who do not have easy access to sewage disposal systems and running water, this is more difficult. If you are travelling to a rural area, or to a country where typhoid may be a problem, it is very important to ensure that all food and water has been properly prepared. Buying bottled water may be more expensive, but could be wise health insurance. Typhoid is not the only infection that can be acquired by drinking contaminated water. If you cook local food yourself, make sure it is properly cooked. In the case of fruit and vegetables: "peel it, boil it or forget it".

Vaccines are available, and are reasonably effective. Some countries require that you be vaccinated against typhoid before you visit them, and in other cases it may be wise to have the vaccine in any case. It is best to consult your doctor or a local travel clinic about this. The current vaccine consists of a heat-killed preparation of the organism, which can give up to 90% protection. However, this vaccine is sometime associated with side-effects such as swelling and tenderness at the injection site, fever and generally felling ill.

There is another vaccine that contains only a part of the organism (i.e. a subunit vaccine), which is slightly less effective than the heat-killed preparation, but has fewer side-effects. Thirdly, there is a live vaccine that is given orally. The organism has been modified so that it does not cause disease, but is able to stimulate your immune system. Side-effects are again relatively mild, potentially consisting of nausea, vomiting and a rash.

When to call the doctor
Typhoid is a serious infection, and the earlier it is diagnosed, the better the outcome is likely to be. Unfortunately, as discussed above, diagnosis can be difficult. If you have a persistent fever and severe headache, it would be advisable to consult your doctor. This is particularly true if you have been travelling in countries where typhoid is common, if you have eaten any unusual foods or eaten in areas where hygiene may be poor. The lack of any gastrointestinal symptoms (such as diarrhoea or nausea) does not exclude typhoid fever as a possibility. Generally speaking, if you have typhoid, you will feel so ill that you will have to see a doctor, but if in doubt, it is advisable to consult one anyway.

Written by Dr Andrew Whitelaw, MBBCh (Witwatersarnd), MSc (UCT), FCPath (Micro) (SA) Senior pathologist, Department of Microbiology, University of Cape Town and National Health Laboratory Service.


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