Typhoid fever, also known simply as typhoid, is a common worldwide bacterial disease transmitted by the ingestion of food or water contaminated with the feces of an infected person, which contain the bacterium Salmonella enterica enterica, serovar Typhi.
The disease has received various names, such as gastric fever, abdominal typhus, infantile remittant fever, slow fever, nervous fever and pythogenic fever.
The name typhoid means "resembling typhus" and comes from the neuropsychiatric symptoms common to typhoid and typhus.
Despite this similarity of their names, typhoid fever and typhus are distinct diseases and are caused by different species of bacteria.
The impact of this disease fell sharply in the developed world with the application of 20th-century sanitation techniques.
In the first week, the temperature rises slowly, and fever fluctuations are seen with relative bradycardia, malaise, headache, and cough.
A bloody nose (epistaxis) is seen in a quarter of cases, and abdominal pain is also possible. There is a decrease in the number of circulating white blood cells (leukopenia) with eosinopenia and relative lymphocytosis; blood cultures are positive for Salmonella typhi or paratyphi. The Widal test is negative in the first week.
In the second week of the infection, the patient lies prostrate with high fever in plateau around 40 °C (104 °F) and bradycardia (sphygmothermic dissociation or Faget sign), classically with a dicrotic pulse wave.
Delirium is frequent, frequently calm, but sometimes agitated. This delirium gives to typhoid the nickname of "nervous fever". Rose spots appear on the lower chest and abdomen in around a third of patients. There are rhonchi in lung bases.
The abdomen is distended and painful in the right lower quadrant, where borborygmi can be heard. Diarrhea can occur in this stage: six to eight stools in a day, green, comparable to pea soup, with a characteristic smell.
However, constipation is also frequent. The spleen and liver are enlarged (hepatosplenomegaly) and tender, and there is elevation of liver transaminases. The Widal test is strongly positive, with antiO and antiH antibodies.
Blood cultures are sometimes still positive at this stage. (The major symptom of this fever is that the fever usually rises in the afternoon up to the first and second week.)
In the third week of typhoid fever, a number of complications can occur:
Public education campaigns encouraging people to wash their hands after defecating and before handling food are an important component in controlling spread of the disease.
According to statistics from the United States Centers for Disease Control and Prevention (CDC), the chlorination of drinking water has led to dramatic decreases in the transmission of typhoid fever in the U.S.A.
A person may become an asymptomatic carrier of typhoid fever, suffering no symptoms, but capable of infecting others. According to the CDC, approximately 5% of people who contract typhoid continue to carry the disease after they recover.
The most famous asymptomatic carrier was Mary Mallon (commonly known as "Typhoid Mary"), a young cook who was responsible for infecting at least 53 people with typhoid, three of whom died from the disease.
Mallon was the first apparently perfectly healthy person known to be responsible for a typhoid "epidemic".
In the early 20th century, many carriers of typhoid were locked into an isolation ward, never to be released, to prevent further typhoid cases. These people often deteriorated mentally, driven mad by the conditions they lived in.
The CFTR protein is present in both the lungs and the intestinal epithelium, and the mutant cystic fibrosis form of the CFTR protein prevents entry of the typhoid bacterium into the body through the intestinal epithelium.
However, the heterozygous advantage hypothesis was proposed in one review in which the author himself writes, "Although cellular/molecular evidence presently is not available for this hypothesis, the CF mutation may be one of several mutations that have spread in European populations because they increased resistance to infectious diseases."
Since no molecular experimental evidence has been presented in support of this theory, this theory is not accepted by the majority of the scientific community.
The Widal test is time-consuming, and often, when a diagnosis is reached, it is too late to start an antibiotic regimen.
The term enteric fever is a collective term that refers to typhoid and paratyphoid.
A 1939 conceptual illustration showing various ways that typhoid bacteria can contaminate a water well (center)
Sanitation and hygiene are the critical measures that can be taken to
prevent typhoid. Typhoid does not affect animals, and therefore,
transmission is only from human to human.
Typhoid can only spread in environments where human feces or urine are able to come into contact with food or drinking water. Careful food preparation and washing of hands are crucial to prevent typhoid.
There are two vaccines licensed for use for the prevention of typhoid: the live, oral Ty21a vaccine (sold as Vivotif Berna) and the injectable Typhoid polysaccharide vaccine (sold as Typhim Vi by Sanofi Pasteur and Typherix by GlaxoSmithKline).
Both are 50% to 80% protective and are recommended for travellers to areas where typhoid is endemic. Boosters are recommended every five years for the oral vaccine and every two years for the injectable form.
There exists an older, killed-whole-cell vaccine that is still used in countries where the newer preparations are not available, but this vaccine is no longer recommended for use because it has a higher rate of side effects (mainly pain and inflammation at the site of the injection).
Where resistance is uncommon, the treatment of choice is a fluoroquinolone such as ciprofloxacin. Otherwise, a third-generation cephalosporin such as ceftriaxone or cefotaxime is the first choice. Cefixime is a suitable oral alternative.
Typhoid fever in most cases is not fatal. Antibiotics, such as ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, amoxicillin and ciprofloxacin, have been commonly used to treat typhoid fever in microbiology (Baron S et al.). Treatment of the disease with antibiotics reduces the case-fatality rate to approximately 1%.
When untreated, typhoid fever persists for three weeks to a month. Death occurs in between 10% and 30% of untreated cases. In some communities, however, case-fatality rates may reach as high as 47%
The disease has received various names, such as gastric fever, abdominal typhus, infantile remittant fever, slow fever, nervous fever and pythogenic fever.
The name typhoid means "resembling typhus" and comes from the neuropsychiatric symptoms common to typhoid and typhus.
Despite this similarity of their names, typhoid fever and typhus are distinct diseases and are caused by different species of bacteria.
The impact of this disease fell sharply in the developed world with the application of 20th-century sanitation techniques.
Signs and symptoms
Classically, the course of untreated typhoid fever is divided into four individual stages, each lasting approximately one week.In the first week, the temperature rises slowly, and fever fluctuations are seen with relative bradycardia, malaise, headache, and cough.
A bloody nose (epistaxis) is seen in a quarter of cases, and abdominal pain is also possible. There is a decrease in the number of circulating white blood cells (leukopenia) with eosinopenia and relative lymphocytosis; blood cultures are positive for Salmonella typhi or paratyphi. The Widal test is negative in the first week.
In the second week of the infection, the patient lies prostrate with high fever in plateau around 40 °C (104 °F) and bradycardia (sphygmothermic dissociation or Faget sign), classically with a dicrotic pulse wave.
Delirium is frequent, frequently calm, but sometimes agitated. This delirium gives to typhoid the nickname of "nervous fever". Rose spots appear on the lower chest and abdomen in around a third of patients. There are rhonchi in lung bases.
The abdomen is distended and painful in the right lower quadrant, where borborygmi can be heard. Diarrhea can occur in this stage: six to eight stools in a day, green, comparable to pea soup, with a characteristic smell.
However, constipation is also frequent. The spleen and liver are enlarged (hepatosplenomegaly) and tender, and there is elevation of liver transaminases. The Widal test is strongly positive, with antiO and antiH antibodies.
Blood cultures are sometimes still positive at this stage. (The major symptom of this fever is that the fever usually rises in the afternoon up to the first and second week.)
In the third week of typhoid fever, a number of complications can occur:
- Intestinal hemorrhage due to bleeding in congested Peyer's patches; this can be very serious but is usually not fatal.
- Intestinal perforation in the distal ileum: this is a very serious complication and is frequently fatal. It may occur without alarming symptoms until septicaemia or diffuse peritonitis sets in.
- Encephalitis
- Neuropsychiatric symptoms (described as "muttering delirium" or "coma vigil"), with picking at bedclothes or imaginary objects.
- Metastatic abscesses, cholecystitis, endocarditis and osteitis
Transmission
The bacterium that causes typhoid fever may be spread through poor hygiene habits and public sanitation conditions, and sometimes also by flying insects feeding on feces.Public education campaigns encouraging people to wash their hands after defecating and before handling food are an important component in controlling spread of the disease.
According to statistics from the United States Centers for Disease Control and Prevention (CDC), the chlorination of drinking water has led to dramatic decreases in the transmission of typhoid fever in the U.S.A.
A person may become an asymptomatic carrier of typhoid fever, suffering no symptoms, but capable of infecting others. According to the CDC, approximately 5% of people who contract typhoid continue to carry the disease after they recover.
The most famous asymptomatic carrier was Mary Mallon (commonly known as "Typhoid Mary"), a young cook who was responsible for infecting at least 53 people with typhoid, three of whom died from the disease.
Mallon was the first apparently perfectly healthy person known to be responsible for a typhoid "epidemic".
In the early 20th century, many carriers of typhoid were locked into an isolation ward, never to be released, to prevent further typhoid cases. These people often deteriorated mentally, driven mad by the conditions they lived in.
Possible protective effects of heterozygosity for cystic fibrosis
It has been hypothesized that cystic fibrosis may have risen to its present levels (1 in 2,500 in the UK) due to the heterozygous advantage that it confers against typhoid fever.The CFTR protein is present in both the lungs and the intestinal epithelium, and the mutant cystic fibrosis form of the CFTR protein prevents entry of the typhoid bacterium into the body through the intestinal epithelium.
However, the heterozygous advantage hypothesis was proposed in one review in which the author himself writes, "Although cellular/molecular evidence presently is not available for this hypothesis, the CF mutation may be one of several mutations that have spread in European populations because they increased resistance to infectious diseases."
Since no molecular experimental evidence has been presented in support of this theory, this theory is not accepted by the majority of the scientific community.
Diagnosis
Diagnosis is made by any blood, bone marrow or stool cultures and with the Widal test (demonstration of salmonella antibodies against antigens O-somatic and H-flagellar). In epidemics and less wealthy countries, after excluding malaria, dysentery or pneumonia, a therapeutic trial time with chloramphenicol is generally undertaken while awaiting the results of the Widal test and cultures of the blood and stool.The Widal test is time-consuming, and often, when a diagnosis is reached, it is too late to start an antibiotic regimen.
The term enteric fever is a collective term that refers to typhoid and paratyphoid.
Prevention
Main article: Typhoid vaccine
Typhoid can only spread in environments where human feces or urine are able to come into contact with food or drinking water. Careful food preparation and washing of hands are crucial to prevent typhoid.
There are two vaccines licensed for use for the prevention of typhoid: the live, oral Ty21a vaccine (sold as Vivotif Berna) and the injectable Typhoid polysaccharide vaccine (sold as Typhim Vi by Sanofi Pasteur and Typherix by GlaxoSmithKline).
Both are 50% to 80% protective and are recommended for travellers to areas where typhoid is endemic. Boosters are recommended every five years for the oral vaccine and every two years for the injectable form.
There exists an older, killed-whole-cell vaccine that is still used in countries where the newer preparations are not available, but this vaccine is no longer recommended for use because it has a higher rate of side effects (mainly pain and inflammation at the site of the injection).
Medical treatment
The rediscovery of oral rehydration therapy in the 1960s provided a simple way to prevent many of the deaths of diarrheal diseases in general.Where resistance is uncommon, the treatment of choice is a fluoroquinolone such as ciprofloxacin. Otherwise, a third-generation cephalosporin such as ceftriaxone or cefotaxime is the first choice. Cefixime is a suitable oral alternative.
Typhoid fever in most cases is not fatal. Antibiotics, such as ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, amoxicillin and ciprofloxacin, have been commonly used to treat typhoid fever in microbiology (Baron S et al.). Treatment of the disease with antibiotics reduces the case-fatality rate to approximately 1%.
When untreated, typhoid fever persists for three weeks to a month. Death occurs in between 10% and 30% of untreated cases. In some communities, however, case-fatality rates may reach as high as 47%
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