Source:  TYPHOID FEVER    Tag:  epidemic typhus symptoms

Typhoid fever
Classification and external resources

Rose spots on the chest of a patient with typhoid fever due to the bacterium SalmonellaTyphi
ICD-10 A01.0
ICD-9 002
DiseasesDB 27829
eMedicine oph/686 med/2331
MeSH D014435
Typhoid fever, also known as  Typhoid, [1] 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, serovar Typhi. [2] [3] The bacteria then perforate through the intestinal wall and are  phagocytosed by macrophages. The organism is a  Gram-negative short bacillus that is motile due to its peritrichous  flagella. The bacterium grows best at 37°C / 98.6°F – human body temperature.
This fever received various names, such as  gastric fever, abdominal typhusinfantile remittant feverslow fever, nervous feverpythogenic fever, etc. The name of "typhoid" comes from the neuropsychiatric symptoms common to typhoid and  typhus (from Greek τῦϕος, "stupor"). [4]
The impact of this disease fell sharply with the application of modern sanitation techniques.



[edit]Signs and symptoms

Typhoid fever is characterized by a slowly progressive  fever as high as  40 °C  (104 °F), profuse sweating and gastroenteritis. Less commonly, a  rash of flat, rose-colored spots may appear. [5]
Classically, the course of untreated typhoid fever is divided into four individual stages, each lasting approximately one week. In the first week, there is a slowly rising temperature with relative  bradycardiamalaise, headache, and cough. A bloody nose ( epistaxis) is seen in a quarter of cases and abdominal pain is also possible. There is leukopenia, a decrease in the number of circulating white blood cells, with  eosinopenia and relative lymphocytosis, a positive reaction and blood cultures are positive for  Salmonella typhi or  paratyphi. The classic 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), 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 with a characteristic smell, comparable to pea soup. However, constipation is also frequent. The spleen and liver are enlarged ( hepatosplenomegaly) and tender, and there is elevation of liver  transaminases. The  Widal reaction 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:
The fever is still very high and oscillates very little over 24 hours.  Dehydration ensues and the patient is delirious (typhoid state). By the end of third week the fever has started reducing this ( defervescence). This carries on into the fourth and final week.


The bacteria which 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. [6] Mallon was the first apparently perfectly healthy person known to be responsible for an "epidemic".
Many carriers of typhoid were locked into an isolation ward never to be released in order to prevent further typhoid cases. These people often deteriorated mentally, driven mad by the conditions they lived in. [7]

[edit]Possible protective effects of heterozygosity for cystic fibrosis

It has been hypothesized that  cystic fibrosis may have risen to its present levels (1 in 1600 in UK) due to the heterozygous advantage that it confers against typhoid fever. [8] 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. '

[edit]Diagnosis of typhoid

Diagnosis is made by any  bloodbone 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  malariadysentery or  pneumonia, a therapeutic trial time with  chloramphenicol is generally undertaken while awaiting the results of  Widal test and cultures of the blood and stool. [9]
The  Widal test is time consuming and often times, 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. [10]


Doctor administering a typhoid vaccination at a school in  San Augustine County, Texas
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 preventing 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 between 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).


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 [10] [12] otherwise, a third-generation cephalosporin such as  ceftriaxone or cefotaxime is the first choice. [13] [14] [15]  Cefixime is a suitable oral alternative.
Typhoid fever in most cases is not fatal.  Antibiotics, such as  ampicillinchloramphenicoltrimethoprim-sulfamethoxazoleamoxicillin and  ciprofloxacin, have been commonly used to treat typhoid fever in developed countries. Prompt 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 [citation needed]. In some communities, however, case-fatality rates may reach as high as 47%. [citation needed]


Resistance to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole and  streptomycin is now common, and these agents have not been used as first line treatment now for almost 20 years. [citation needed] Typhoid that is resistant to these agents is known as multidrug-resistant typhoid (MDR typhoid).
Ciprofloxacin resistance is an increasing problem, especially in the  Indian subcontinent and  Southeast Asia. Many centres are therefore moving away from using ciprofloxacin as first line for treating suspected typhoid originating in South America, India, Pakistan, Bangladesh, Thailand or Vietnam. For these patients, the recommended first line treatment is ceftriaxone. It has also been suggested  azithromycin is better at treating typhoid in resistant populations than both fluoroquinolone drugs and ceftriaxone. [12] Azithromycin significantly reduces relapse rates compared with ceftriaxone.
There is a separate problem with laboratory testing for reduced susceptibility to ciprofloxacin: current recommendations are that isolates should be tested simultaneously against ciprofloxacin (CIP) and against nalidixic acid (NAL), and that isolates that are sensitive to both CIP and NAL should be reported as "sensitive to ciprofloxacin", but that isolates testing sensitive to CIP but not to NAL should be reported as "reduced sensitivity to ciprofloxacin". However, an analysis of 271 isolates showed that around 18% of isolates with a reduced susceptibility to ciprofloxacin ( MIC 0.125–1.0 mg/l) would not be picked up by this method. [18] It is not certain how this problem can be solved, because most laboratories around the world (including the West) are dependent on  disk testing and cannot test for MICs.


Incidence of typhoid fever
 Strongly  endemic
 Sporadic cases
Death rates for typhoid fever in the U.S. 1906–1960
With an estimated 16–33 million cases of annually resulting in 216,000 deaths in endemic areas, the  World Health Organizationidentifies typhoid as a serious public health problem. Its incidence is highest in children and young adults between 5 and 19 years old. [19]


Around 430–424 BC, a devastating  plague, which some believe to have been typhoid fever, killed one third of the population of  Athens, including their leader  Pericles. The balance of power shifted from Athens to  Sparta, ending the  Golden Age of Pericles that had marked Athenian dominance in the Greek ancient world. Ancient historian Thucydides also contracted the disease, but he survived to write about the plague. His writings are the primary source on this outbreak and modern academics and medical scientists consider  epidemic typhus the most likely cause; a 2006 study detected  DNA sequences similar to those of the bacterium responsible for typhoid fever. [20]However the cause of the plague has long been disputed and other scientists have disputed the findings, citing serious methodologic flaws in the dental pulp-derived DNA study. [21] The disease is most commonly transmitted through poor hygiene habits and public sanitation conditions; during the period in question, the whole population of  Attica was besieged within the  Long Walls and lived in tents.
Mary Mallon ("Typhoid Mary") in a hospital bed (foreground). She was forcibly quarantined as a carrier of typhoid fever in 1907 for three years and then again from 1915 until her death in 1938.
Some historians believe that in the English colony of  Jamestown, Virginia, typhoid fever killed more than 6000 settlers between 1607 and 1624. [22] During the  American Civil War, 81,360 Union soldiers died of typhoid or  dysentery. [23] In the late 19th century,  typhoid fever mortality rate in Chicago averaged 65 per 100,000 people a year. The worst year was 1891, when the typhoid death rate was 174 per 100,000 people. [24] The most notorious carrier of typhoid fever—but by no means the most destructive—was  Mary Mallon, also known as Typhoid Mary. In 1907, she became the first  American carrier to be identified and traced. She was a cook in  New York. She is closely associated with fifty-three cases and three deaths. [25] Public health authorities told Mary to give up working as a cook or have her  gall bladder removed. Mary quit her job but returned later under a  false name. She was detained and  quarantined after another typhoid outbreak. She died of pneumonia after 26 years in quarantine.
In 1880 Karl Joseph Eberth described a bacillus that he suspected was the cause of typhoid. In 1884 pathologist Georg Theodor August Gaffky (1850–1918) confirmed Eberth's findings, and the organism was given names such as Eberth's bacillus, Eberthella typhi and Gaffky-Eberth bacillus. Today the bacillus that causes typhoid fever goes by the scientific name of  Salmonella enterica enterica, serovar Typhi.
Almroth Edward Wright developed an effective inactivated whole-cell typhoid vaccine that was introduced in 1896. [11] In 1909,  Frederick F. Russell, a  U.S. Army physician, developed an American typhoid vaccine and two years later his vaccination program became the first in which an entire army was immunized. It eliminated typhoid as a significant cause of morbidity and mortality in the U.S. military.
Most developed countries saw declining rates of typhoid fever throughout the first half of the 20th century due to vaccinations and advances in public sanitation and hygiene. Antibiotics were introduced in clinical practice in 1942, greatly reducing mortality. Today, incidence of typhoid fever in developed countries is around 5 cases per 1,000,000 people per year.
An outbreak in the  Democratic Republic of Congo in 2004–05 recorded more than 42,000 cases and 214 deaths.
Typhoid fever was also known as  suette milliaire in nineteenth-century France.

Famous victims

Lizzie van Zyl was a child inmate in a British-run concentration camp in South Africa who died from typhoid fever during the  Boer War (1899–1902).
Famous people who have had the disease include