Medicine for Africa - Medical Information Service

YPHOID FEVER

Definition:

Typhoid fever, which is also known under the names of ‘enteric fever’ or ‘bilious fever’, is an acute intestinal illness, caused by the bacterium ‘Salmonella enterica’ (S. enterica) of the serotype Typhi. The S. typhi bacterium is present worldwide and usually transmitted by ingestion of feces-contaminated food products or water/beverages. S. typhi is a gram-negative short motile bacillus, due to its peritrichous (having flagellae around its entire surface) flagellae (long, slender projections from the cell body, for the purpose of moving the bacterium forward).

The bacteria enter the blood stream where they multiply (they grow best at temperatures of about 37ºC or 98.6ºF, the normal human body’s temperature), and which carries them towards the intestinal tract where they locate, and from where they may be excreted in large numbers, resulting in the spread of the infection.  There is also a so-called carrier stage that can vary from days to years, and about three percent of patients can go on to remain lifelong carriers of the bacterium, thus, being a lifelong potential source of spreading the disease, especially in an environment of poor hygienic measure.

S. typhi can also be transmitted in the presence of poor hygienic measures (cave: washing hands!) by flying insects which feed on feces, or live in areas of insufficient sewage installations, prior to ‘visiting’ human residential areas.  S. typhi lives only in humans, and can also be transmitted among infected humans – actively infected or non-actively infected persons, the so-called ‘asymptomatic carriers’, who may not present with any symptoms anymore, following a healed infection, yet still harbor sufficient bacteria to infect close contact people, if the surrounding hygiene habits are poor.  The illness is common in developing countries, where it infects close to 22 million people annually.  It is also present in slums and following certain natural catastrophes, such as e.g. flooding or cyclones, with subsequent serious sewage problems.

         Historic Review

The first major epidemic has been described following the fall of Athens at around 430 B.C. and subsequent power shift to Sparta, resulting in a devastating plague hitting Athens, which was believed to be typhoid fever.

The first effective vaccine had been developed in 1897 by Sir Almroth Edward Wright, a British bacteriologist and immunologist, who developed his vaccine which consisted of heat-killed typhoid bacilli.

Famous victims who succumbed of typhoid fever include, among many others:

• Franz Peter Schubert, Austrian composer, in 1828;
• Albert of Saxen-Coburg-Gotha – Queen Victoria’s husband, in 1861;
• President Abraham Lincoln’s son, Willie, in 1862;
• Gerard Manley Hopkins, an English poet (Beowulf, As Kingfishers Catch Fire, and many more), in 1889; 
• Archduke Karl Ludwig of Austria in 1896, and
• Wilbur Wright, one of the Wright brothers, and first aviator in modern history, in 1912.

Symptoms:

Characteristic features of typhoid fever include a high, sustained fever of as much as 40ºC (104ºF), accompanied by profuse sweating, gastrointestinal symptomatology such as diarrhea, as well as a fairly characteristic rash of flat, rose-colored spots on the lower chest and/or abdomen.  The rising temperature is usually accompanied by bradycardia (low heart rate, below 60 beats per minute at rest), general feeling of malaise, cough and headaches.  Frequent epistaxis (nosebleed) and abdominal pains are seen in up to 25% of cases.

During the second week of infection, the patient often develops a state of calm or agitated delirium, which gave the disease its common name of ‘nervous fever’.  Now, the abdomen becomes distended and painful, characteristically in the right lower quadrant (cave differential diagnosis of acute appendicitis), where stomach growling or rumbling (borborygmi) can be heard.  At this stage of the disease, diarrhea with six to eight and even more bowel movements a day can occur, with a characteristic green colored, ‘pea-soup’ like smell of the stool.  On the other hand, there may also be constipation.  Both liver and spleen will be enlarged (hepatosplenomegaly) and tender to the touch.  

In the third week, untreated patients will continue to progress and develop complications, such as serious, occasionally even fatal, intestinal bleeding, perforation of the distal small intestine (ileum), which may be associated with septicemia and/or diffuse peritonitis.  Other complications include cholecystitis (inflammation of the gall bladder), encephalitis (an acute inflammation of the brain), endocarditis (inflammation of the cardiac sac), and osteitis (inflammation of the bones).

Subsequent dehydration may push the patient into delirium and result in the patient’s death.  Defervescence (abatement of fever) will stretch the disease into its fourth week.
                  

Diagnosis:

The so-called ‘Widal test’, demonstrating specific antibodies in the blood against salmonella produced antigens ‘O-somatic’ (antiO antibodies) and ‘H-flagellar’ (antiH antibodies), is usually strongly positive in cases of the presence of S. typhi, typhoid fever.

In addition, diagnosis can be made by way of culturing blood, stool or bone marrow samples.  During an epidemic, or in less developed countries with insufficient laboratory capabilities, and subsequent sending out of samples, a therapeutic trial time with prescribing chloramphenicol is often performed, following the exclusion of dysentery, pneumonia and malaria, and while awaiting results of the Widal test or blood cultures.

However, while the Widal test turns positive only during the second week of infection, the ‘diazo reaction’ (red discoloration of the urine following the addition of diazobenzenesulphonic acid [not specific]) may be positive for S. typhi or S. paratyphi.
A complete blood count (CBC) may reveal leukopenia (low white blood cells), with accompanying eosinopenia (low eosinophiles) and resulting relative lymphocytosis (predominance of lymphocytes).   In the second week, liver enzymes, such as AST, ALT and γGT can be elevated, along with a strongly positive Widal test.

 
Treatment:

Usually, typhoid fever is not a fatal disease; it can easily be treated with a range of antibiotics, such as ampicillin, chloramphenicol, ciprofloxacin or trimethoprim-sulfamethoxazole, if treatment is instigated early and compliance is maintained.  

While the fatality rate in treated cases is only about 1%, it can increase to 10% to 30% in untreated cases after weeks or months of disease, or even within no more than one month duration.

As with many antibiotics, resistance to those drugs occurs over time, and typhoid fever has made no exception.  Thus, of the above mentioned drugs, only ciprofloxacin has some antibacterial effects left, with major resistance problems occurring on the Indian subcontinent and in Southeast Asia.  Here, ceftriaxone, a third generation cephalosporin antibiotic drug, is recommended for treatment.

Some typhoid patients may develop into a so-called ‘carrier stage’, usually patients who may not have been treated or not efficiently been treated.  This stage can last from days to many years, during which the patient his/herself appears healthy, but is a continuous source of infection for exposed people.  There are about three percent of typhoid patients, who may even become lifelong carriers of the bacterium, which occurs more often in children than in adults.

 
Prevention:

There is a vaccine available, usually reserved for tourists and travelers to less developed and high risk countries.  Two vaccines, recommended by the World Health Organization (WHO), consist of the live, orally applied Ty21a vaccine (Vivotif Berna®), and the vi capsular polysaccharide vaccine (Typhim Vi®), applied via injection, have a protective effect of somewhere between 50% and 80%. 

The vaccination should be performed at least one week prior to travelling to a high-risk country, and the vaccine is effective for about ten years, before a booster vaccination should be applied.

While typhoid fever only spreads from humans to humans via feces and/or urine exposure, the most important preventive measure is strict attention to sanitation and hygiene (frequent hand washing), and tight food and water precautions (no water rinsed salad, insufficiently cooked vegetables, non-bottled water, or ice cubes in beverages, etc.), when travelling in potentially high risk countries.

Thus – ‘boil it, cook it, peel it, or forget it’ – is always an easy and most effective way to prevent a potential infection with typhoid fever, cholera, and many other diseases that are the result of insufficient sanitary conditions.

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