Typhoid fever

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Jump to: navigation, search For an unrelated disease with a similar name, see typhus. For a related disease which is caused by two different bacteria, see Paratyphoid fever. For the character in the 2005 film Elektra, see Typhoid (Elektra). Typhoid fever, also known as Salmonella Typhi or commonly just typhoid,[1] is an illness. Common worldwide, it is transmitted by the ingestion of food or water contaminated with feces from an infected person.[2] The bacteria then perforate through the intestinal wall and are phagocytosed by macrophages. Salmonella Typhi, more correctly called Salmonella enterica enterica Typhi, then alters its structure to resist destruction and allow them to exist within the macrophage. This renders them resistant to damage by PMN's, complement and the immune response. The organism is then spread via the lymphatics while inside the macrophages. This gives them access to the reticuloendothelial system and then to the different organs throughout the body. The organism is a Gram-negative short bacillus that is motile due to its peritrichous flagella. The bacterium grows best at 37 C/99 F human body temperature.

Symptoms

Incidence of typhoid fever

Strongly endemic Endemic Sporadic cases

Typhoid fever is characterized by a slowly progressive fever as high as 40 C (104 F), profuse sweating, gastroenteritis, and nonbloody diarrhea. Less commonly a rash of flat, rose-colored spots may appear.[3] 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 bradycardia, malaise, 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 diazo 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 prostrated with high fever in plateau around 40 C (104 F) and bradycardia (Sphygmo-thermic 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 1/3 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 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 non-fatal. Intestinal perforation in 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 Metastatic abscesses, cholecystitis, endocarditis and osteitis

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 (defervescence). This carries on into the fourth and final week.

[edit] 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 Widal test and blood cultures.[4] The term "enteric fever" is a collective term that refers to typhoid and paratyphoid.[5]

[edit] Treatment
Where resistance is uncommon, the treatment of choice is a fluoroquinolone such as ciprofloxacin[5][6] otherwise, a third-generation cephalosporin such as ceftriaxone or cefotaxime is the first choice.[7][8][9] Cefixime is a suitable oral alternative.[10][11] 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 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. Though in some communities case-fatality rates may be as high as 47%.

[edit] Resistance
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. 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 0.1251.0 mg/l) would not be picked up by this method.[13] It is not certain how this problem can be solved, because most laboratories around the world (including the West) are dependent on disc testing and cannot test for MICs.

Prevention

Doctor administering a typhoid vaccination at a school in San Augustine County, Texas

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 therefore crucial to preventing typhoid. There are two vaccines currently recommended by the World Health Organization for the prevention of typhoid:[14] these are 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 travelers to

areas where typhoid is endemic. 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).[14]

1939 conceptual illustration showing various ways that typhoid bacteria can contaminate a water well (center)

[edit] Transmission
Flying insects feeding on feces may occasionally transfer the bacteria through poor hygiene habits and public sanitation conditions. 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 Center for Disease Control, the chlorination of drinking water has led to dramatic decreases in the transmission of typhoid fever in the U.S. A person may become an asymptomatic carrier of typhoid fever, suffering no symptoms, but capable of infecting others. According to the Centers for Disease Control 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 an "epidemic".

Death rates for typhoid fever in the U.S. 19061960

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.[15]

[edit] Epidemiology
With an estimated 1633 million cases of annually resulting in 500,000 to 600,000 deaths in endemic areas, the World Health Organization identifies typhoid as a serious public health problem. Its incidence is highest in children and young adults between 5 and 19 years old.[16]

[edit] Heterozygous advantage

It is thought 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.[17] 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.

[edit] History
Around 430424 B.C., 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 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. The cause of the plague has long been disputed, with modern academics and medical scientists considering epidemic typhus the most likely cause. However, a 2006 study detected DNA sequences similar to those of the bacterium responsible for typhoid fever.[18] Other scientists have disputed the findings, citing serious methodologic flaws in the dental pulpderived DNA study.[19] 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. This fever received various names, such as gastric fever, the bends, abdominal typhus, infantile remittent fever, slow fever, nervous fever, pythogenic fever, etc. The name of " typhoid " was given by Louis in 1829, as a derivative from typhus.

Mary Mallon ("Typhoid Mary") in a hospital bed. 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.

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.[20] The most notorious carrier of typhoid feverbut by no means the most destructivewas 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; some believe she was the source of infection for several hundred people. She is closely associated with forty-seven cases and three deaths.[21] 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 1897, Almroth Edward Wright developed an effective vaccine. 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 200405 recorded more than 42,000 cases and 214 deaths.[16] Typhoid fever was also known as suette milliaire in nineteenth-century France.