Typhoid fever Enteric fever Last reviewed: June 9, 2011.

Typhoid fever is an infection that causes diarrhea and a rash -- most commonly d ue to a type of bacteria called Salmonella typhi (S. typhi). Causes, incidence, and risk factors The bacteria that cause typhoid fever -- S. typhi -- spread through contaminated food, drink, or water. If you eat or drink something that is contaminated, the bacteria enter your body. They travel into your intestines, and then into your b loodstream, where they can get to your lymph nodes, gallbladder, liver, spleen, and other parts of your body. A few people can become carriers of S. typhi and continue to release the bacteri a in their stools for years, spreading the disease. Typhoid fever is common in developing countries, but fewer than 400 cases are re ported in the U.S. each year. Most cases in the U.S. are brought in from other c ountries where typhoid fever is common. Symptoms Early symptoms include fever, general ill-feeling, and abdominal pain. A high (t ypically over 103 degrees Fahrenheit) fever and severe diarrhea occur as the dis ease gets worse. Some people with typhoid fever develop a rash called "rose spots," which are sma ll red spots on the abdomen and chest. Other symptoms that occur include: Abdominal tenderness Agitation Bloody stools Chills Confusion Difficulty paying attention (attention deficit) Delirium Fluctuating mood Hallucinations Nosebleeds Severe fatigue Slow, sluggish, lethargic feeling Weakness Signs and tests

A complete blood count (CBC) will show a high number of white blood cells. A blood culture during the first week of the fever can show S. typhi bacteria. Other tests that can help diagnose this condition include: ELISA urine test to look for the bacteria that cause Typhoid fever Fluorescent antibody study to look for substances that are specific to Typho id bacteria Platelet count (platelet count will be low) Stool culture Treatment Fluids and electrolytes may be given through a vein (intravenously), or you may be asked to drink uncontaminated water with electrolyte packets. Appropriate antibiotics are given to kill the bacteria. There are increasing rat es of antibiotic resistance throughout the world, so your health care provider w ill check current recommendations before choosing an antibiotic. Expectations (prognosis) Symptoms usually improve in 2 to 4 weeks with treatment. The outcome is likely t o be good with early treatment, but becomes poor if complications develop. Symptoms may return if the treatment has not completely cured the infection. Complications Intestinal hemorrhage (severe GI bleeding) Intestinal perforation Kidney failure Peritonitis Calling your health care provider Call your health care provider if: You have had any known exposure to typhoid fever You have been in an endemic area and you develop symptoms of typhoid fever You have had typhoid fever and the symptoms return You develop severe abdominal pain, decreased urine output, or other new symp toms Prevention Vaccines are , Australia, g to an area should bring recommended for travel outside of the U.S., Canada, northern Europe and New Zealand, and during epidemic outbreaks. If you are travelin where there is typhoid fever, ask your health care provider if you electrolyte packets in case you get sick.

Immunization is not always completely effective and at-risk travelers should dri

nk only boiled or bottled water and eat well-cooked food. Studies of an oral liv e attenuated typhoid vaccine are now under way and appear promising. Water treatment, waste disposal, and protecting the food supply from contaminati on are important public health measures. Carriers of typhoid must not be allowed to work as food handlers.

Typhoid fever, also known as typhoid,[1] is a common worldwide illness, transmit ted 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] T he bacteria then perforate through the intestinal wall and are phagocytosed by m acrophages. The organism is a Gram-negative short bacillus that is motile due to its peritrichous flagella. The bacterium grows best at 37C / 98.6F human body tem perature. This fever received various names, such as gastric fever, abdominal typhus, infa ntile remittant fever, slow fever, nervous fever, pythogenic fever, etc. The nam e of "typhoid" comes from the neuropsychiatric symptoms common to typhoid and ty phus (from Greek t????, "stupor").[4] The impact of this disease fell sharply with the application of modern sanitatio n techniques. Contents [hide] 1 Signs and symptoms 2 Transmission 2.1 Possible protective effects of heterozygosity for cystic fibrosis 3 Diagnosis of typhoid 4 Prevention 5 Treatment 5.1 Resistance 6 Epidemiology 7 History 7.1 Famous victims 7.2 In fiction 8 See also 9 References 9.1 Further reading 10 External links Signs and symptoms Typhoid fever is characterized by a slowly progrssive fever as high as 40 C (104 F ), profuse sweating and gastroenteritis. Less commonly, a rash of flat, rose-col ored spots may appear.[5] Classically, the course of untreated typhoid fever is divided into four individu al stages, each lasting approximately one week. In the first week, there is a sl owly rising temperature with relative bradycardia, malaise, headache, and cough. A bloody nose (epistaxis) is seen in a quarter of cases and abdominal pain is a lso possible. There is leukopenia, a decrease in the number of circulating white blood cells, with eosinopenia and relative lymphocytosis, a positive reaction a

nd blood cultures are positive for Salmonella typhi or paratyphi. The classic Wi dal 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), clas sically with a dicrotic pulse wave. Delirium is frequent, frequently calm, but s ometimes 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 patient s. 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 s tage: six to eight stools in a day, green with a characteristic smell, comparabl e to pea soup. However, constipation is also frequent. The spleen and liver are enlarged (hepatosplenomegaly) and tender, and there is elevation of liver transa minases. 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 a nd 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 complicat ion and is frequently fatal. It may occur without alarming symptoms until septic aemia 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 The fever is still very high and oscillates very little over 24 hours. Dehydrati on 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 f ourth and final week. [edit] Transmission Flying insects feeding on feces may occasionally transfer the bacteria through p oor 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 s tatistics from the United States Centers for Disease Control and Prevention (CDC ), the chlorination of drinking water has led to dramatic decreases in the trans mission of typhoid fever in the U.S. A person may become an asymptomatic carrier of typhoid fever, suffering no sympt oms, but capable of infecting others. According to the CDC approximately 5% of p eople who contract typhoid continue to carry the disease after they recover. The most famous asymptomatic carrier was Mary Mallon (commonly known as "Typhoid Ma ry"), a young cook who was responsible for infecting at least 53 people with typ hoid, three of whom died from the disease.[6] Mallon was the first apparently pe rfectly 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 ment ally, 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 leve ls (1 in 1600 in UK) due to the heterozygous advantage that it confers against t yphoid fever.[8] The CFTR protein is present in both the lungs and the intestina

l epithelium, and the mutant cystic fibrosis form of the CFTR protein prevents e ntry of the typhoid bacterium into the body through the intestinal epithelium. H owever, the heterozygous advantage hypothesis was proposed in one review in whic h the author himself writes, "Although cellular/molecular evidence presently is not available for this hypothesis, the CF mutation may be one of several mutatio ns that have spread in European populations because they increased resistance to infectious diseases." Since no molecular experimental evidence has been present ed 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 blood, bone marrow or stool cultures and with the Widal test (demonstration of salmonella antibodies against antigens O-somatic and H-f lagellar). In epidemics and less wealthy countries, after excluding malaria, dys entery or pneumonia, a therapeutic trial time with chloramphenicol is generally undertaken while awaiting the results of Widal test and cultures of the blood an d stool.[9] The Widal test is time consuming and oftentimes when 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 paratyp hoid.[10] [edit] Prevention Main article: Typhoid vaccine Doctor administering a typhoid vaccination at a school in San Augustine County, Texas 1939 conceptual illustration showing various ways that typhoid bacteria can cont aminate a water well (center) Sanitation and hygiene are the critical measures that can be taken to prevent ty phoid. Typhoid does not affect animals and therefore transmission is only from h uman to human. Typhoid can only spread in environments where human feces or urin e are able to come into contact with food or drinking water. Careful food prepar ation and washing of hands are crucial to preventing typhoid. There are two vaccines currently recommended by the World Health Organization fo r the prevention of typhoid:[11] these are the live, oral Ty21a vaccine (sold as Vivotif Berna) and the injectable Typhoid polysaccharide vaccine (sold as Typhi m 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 ende mic. Boosters are recommended every 5 years for the oral vaccine and every 2 yea rs 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 s ide effects (mainly pain and inflammation at the site of the injection).[11] [edit] Treatment The rediscovery of oral rehydration therapy in the 1960s provided a simple way t o 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 cef triaxone or cefotaxime is the first choice.[13][14][15] Cefixime is a suitable o ral alternative.[16][17] Typhoid fever in most cases is not fatal. Antibiotics, such as ampicillin, chlor amphenicol, trimethoprim-sulfamethoxazole, amoxicillin and ciprofloxacin, have b een commonly used to treat typhoid fever in developed countries. Prompt treatmen t of the disease with antibiotics reduces the case-fatality rate to approximatel y 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] [edit] Resistance Resistance to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole and str eptomycin is now common, and these agents have not been used as first line treat ment now for almost 20 years.[citation needed] Typhoid that is resistant to thes e agents is known as multidrug-resistant typhoid (MDR typhoid). Ciprofloxacin resistance is an increasing problem, especially in the Indian subc ontinent and Southeast Asia. Many centres are therefore moving away from using c iprofloxacin as first line for treating suspected typhoid originating in South A merica, India, Pakistan, Bangladesh, Thailand or Vietnam. For these patients, th e recommended first line treatment is ceftriaxone. It has also been suggested az ithromycin is better at treating typhoid in resistant populations than both fluo roquinolone drugs and ceftriaxone.[18] Azithromycin significantly reduces relaps e rates compared with ceftriaxone. There is a separate problem with laboratory testing for reduced susceptibility t o ciprofloxacin: current recommendations are that isolates should be tested simu ltaneously against ciprofloxacin (CIP) and against nalidixic acid (NAL), and tha t isolates that are sensitive to both CIP and NAL should be reported as "sensiti ve to ciprofloxacin", but that isolates testing sensitive to CIP but not to NAL should be reported as "reduced sensitivity to ciprofloxacin". However, an analys is of 271 isolates showed that around 18% of isolates with a reduced susceptibil ity to ciprofloxacin (MIC 0.125 1.0 mg/l) would not be picked up by this method.[1 9] It is not certain how this problem can be solved, because most laboratories a round the world (including the West) are dependent on disk testing and cannot te st for MICs. [edit] Epidemiology Incidence of typhoid fever ? Strongly endemic ? 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 e ndemic areas, the World Health Organization identifies typhoid as a serious publ ic health problem. Its incidence is highest in children and young adults between 5 and 19 years old.[20] [edit] History Around 430 424 BC, a devastating plague, which some believe to have been typhoid f ever, killed one third of the population of Athens, including their leader Peric les. The balance of power shifted from Athens to Sparta, ending the Golden Age o f Pericles that had marked Athenian dominance in the ancient world. Ancient hist orian Thucydides also contracted the disease, but he survived to write about the plague. His writings are the primary source on this outbreak and modern academi cs 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.[21] However the cause of the plague has long been disputed and ot her scientists have disputed the findings, citing serious methodologic flaws in the dental pulp-derived DNA study.[22] 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 a nd lived in tents. Mary Mallon ("Typhoid Mary") in a hospital bed (foreground). She was forcibly qu arantined as a carrier of typhoid fever in 1907 for three years and then again f

rom 1915 until her death in 1938. Some historians believe that in the English colony of Jamestown, Virginia, typho id fever killed more than 6000 settlers between 1607 and 1624.[23] During the Am erican Civil War, 81,360 Union soldiers died of typhoid or dysentery.[24] 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.[25] The most notorious carrier of typhoid fever but by no mean s the most destructive was Mary Mallon, also known as Typhoid Mary. In 1907, she b ecame 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.[26] Public health authorities told Mary to give up working as a cook or have her ga ll 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 pneumo nia 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, E berthella typhi and Gaffky-Eberth bacillus. Today the bacillus that causes typho id fever goes by the scientific name of Salmonella enterica enterica, serovar Ty phi. In 1897, Almroth Edward Wright developed an effective vaccine. In 1909, Frederic k F. Russell, a U.S. Army physician, developed an American typhoid vaccine and t wo 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 mor tality in the U.S. military. Most developed countries saw declining rates of typhoid fever throughout the fir st half of the 20th century due to vaccinations and advances in public sanitatio n 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 42,0 00 cases and 214 deaths.[20] Typhoid fever was also known as suette milliaire in nineteenth-century France.