Typhoid fever, also known simply as typhoid, is a bacterial infection due to Salmonella typhi that causes symptoms. Symptoms may vary from mild to severe and usually begin six to thirty days after exposure. Often there is a gradual onset of a high fever over several days; weakness, abdominal pain, constipation, headaches, and mild vomiting also commonly occur. Some people develop a skin rash with rose colored spots. In severe cases there may be confusion. Without treatment, symptoms may last weeks or months. Diarrhea is uncommon. Other people may carry the bacterium without being affected; however, they are still able to spread the disease to others. Typhoid fever is a type of enteric fever, along with paratyphoid fever.
The cause is the bacterium Salmonella Typhi, also known as Salmonella enterica serotype Typhi, growing in the intestines and blood. Typhoid is spread by eating or drinking food or water contaminated with the feces of an infected person. Risk factors include poor sanitation and poor hygiene. Those who travel in the developing world are also at risk. Only humans can be infected. Symptoms are similar to those of many other infectious diseases. Diagnosis is by either culturing the bacteria or detecting the bacterium's DNA in the blood, stool, or bone marrow. Culturing the bacterium can be difficult. Bone marrow testing is the most accurate.
A typhoid vaccine can prevent about 40% to 90% of cases during the first two years. The vaccine may have some effect for up to seven years. It is recommended for those at high risk or people traveling to areas where the disease is common. Other efforts to prevent the disease include providing clean drinking water, good sanitation, and handwashing. Until it has been confirmed that an individual's infection is cleared, the individual should not prepare food for others. The disease is treated with antibiotics such as azithromycin, fluoroquinolones or third generation cephalosporins. Resistance to these antibiotics has been developing, which has made treatment of the disease more difficult.
In 2015, there were 12.5 million new cases worldwide. The disease is most common in India. Children are most commonly affected. Rates of disease decreased in the developed world in the 1940s as a result of improved sanitation and use of antibiotics to treat the disease. Each year in the United States, about 400 cases are reported and it is estimated that the disease occurs in about 6,000 people. In 2015, it resulted in about 149,000 deaths worldwide – down from 181,000 in 1990 (about 0.3% of the global total). The risk of death may be as high as 20% without treatment. With treatment, it is between 1 and 4%. Typhus is a different disease. However, the name typhoid means "resembling typhus" due to the similarity in symptoms.
|Synonyms||Slow fever, typhoid|
|Rose spots on the chest of a person with typhoid fever|
|Symptoms||Fever, abdominal pain, headache, rash|
|Usual onset||6–30 days after exposure|
|Causes||Salmonella typhi (spread by food or water contaminated with feces)|
|Risk factors||Poor sanitation, poor hygiene.|
|Diagnostic method||Bacterial culture, DNA detection|
|Differential diagnosis||Other infectious diseases|
|Prevention||Typhoid vaccine, handwashing|
|Frequency||12.5 million (2015)|
Classically, the course of untreated typhoid fever is divided into four distinct stages, each lasting about a week. Over the course of these stages, the patient becomes exhausted and emaciated.
The Gram-negative bacterium that causes typhoid fever is Salmonella Typhi, also known as Salmonella enterica serotype Typhi. There are two main types of Typhi namely the ST1 and ST2 based on MLST subtyping scheme, which are currently widespread globally.
Salmonella Typhi is spread through the fecal-oral route from individuals that are currently infected and from asymptomatic carriers of the bacteria. Unlike other strains of Salmonella, there are no animal carriers of S. Typhi. Humans are the only known carriers of the bacteria. An asymptomatic human carrier is an individual who is still excreting S. Typhi in their stool a year after the acute stage of the infection. Human carriers are responsible for the transmission of the bacteria in endemic regions of the world.
Diagnosis is made by any blood, bone marrow or stool cultures and with the Widal test (demonstration of antibodies against Salmonella 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 prone to significant false positive results. The test may also be falsely negative in the early course of illness. However, unlike the Typhidot test, the Widal test quantifies the specimen with titres.
Typhidot is a medical test consisting of a dot ELISA kit that detects IgM and IgG antibodies against the outer membrane protein (OMP) of the Salmonella typhi. The typhidot test becomes positive within 2–3 days of infection and separately identifies IgM and IgG antibodies. The test is based on the presence of specific IgM and IgG antibodies to a specific 50Kd OMP antigen, which is impregnated on nitrocellulose strips. IgM shows recent infection whereas IgG signifies remote infection. The most important limitation of this test is that it is not quantitative and the result is only positive or negative.
The term 'enteric fever' is a collective term that refers to severe typhoid and paratyphoid.
Sanitation and hygiene are important to prevent typhoid. Typhoid does not affect animals other than humans. Typhoid can only spread in environments where human feces are able to come into contact with food or drinking water. Careful food preparation and washing of hands are crucial to prevent typhoid. Industrialization, and in particular, the invention of the automobile, contributed greatly to the elimination of typhoid fever, as it eliminated the public health hazards associated with having horse manure in the public street which led to large number of flies. 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 United States.
Two typhoid vaccines are licensed for use for the prevention of typhoid: the live, oral Ty21a vaccine (sold as Vivotif by Crucell Switzerland AG) and the injectable typhoid polysaccharide vaccine (sold as Typhim Vi by Sanofi Pasteur and 'Typherix by GlaxoSmithKline). Both are efficacious and 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. An older, killed-whole-cell vaccine 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).
To help decrease rates of typhoid fever in developing nations, the World Health Organization (WHO) endorsed the use of a vaccination program starting in 1999. Vaccinations have proven to be a great way at controlling outbreaks in high incidence areas. Just as important, it is also very cost-effective. Vaccination prices are normally low, less than US $1 per dose. Because the price is low, poverty-stricken communities are more willing to take advantage of the vaccinations. Although vaccination programs for typhoid have proven to be effective, they alone cannot eliminate typhoid fever. Combining the use of vaccines along with increasing public health efforts is the only proven way to control this disease.
Since the 1990s there have been two typhoid fever vaccines recommended by the World Health Organization. The ViPS vaccine is given via injection, while the Ty21a is taken through capsules. It is recommended only people 2 years or older be vaccinated with the ViPS vaccine and requires a revaccination after 2–3 years with a 55–72% vaccine efficacy. The alternative Ty21a vaccine is recommended for people 5 years or older, and has a 5-7-year duration with a 51–67% vaccine efficacy. The two different vaccines have been proven as a safe and effective treatment for epidemic disease control in multiple regions.
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, when properly treated, is not fatal in most cases. Antibiotics, such as ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, amoxicillin, and ciprofloxacin, have been commonly used to treat typhoid fever in microbiology. Treatment of the disease with antibiotics reduces the case-fatality rate to about 1%.
Without treatment, some patients develop sustained fever, bradycardia, hepatosplenomegaly, abdominal symptoms and, occasionally, pneumonia. In white-skinned patients, pink spots, which fade on pressure, appear on the skin of the trunk in up to 20% of cases. In the third week, untreated cases may develop gastrointestinal and cerebral complications, which may prove fatal in up to 10–20% of cases. The highest case fatality rates are reported in children under 4 years. Around 2–5% of those who contract typhoid fever become chronic carriers, as bacteria persist in the biliary tract after symptoms have resolved.
Surgery is usually indicated in cases of intestinal perforation. Most surgeons prefer simple closure of the perforation with drainage of the peritoneum. Small-bowel resection is indicated for patients with multiple perforations.
If antibiotic treatment fails to eradicate the hepatobiliary carriage, the gallbladder should be resected. Cholecystectomy is not always successful in eradicating the carrier state because of persisting hepatic infection.
As resistance to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, and streptomycin is now common, these agents have not been used as first–line treatment of typhoid fever for almost 20 years. Typhoid 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 shifting from using ciprofloxacin as the first line for treating suspected typhoid originating in South America, India, Pakistan, Bangladesh, Thailand, or Vietnam. For these people, the recommended first-line treatment is ceftriaxone. Also, azithromycin has been suggested to be better at treating typhoid in resistant populations than both fluoroquinolone drugs and ceftriaxone. Azithromycin significantly reduces relapse rates compared with ceftriaxone.
A separate problem exists 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. How this problem can be solved is not certain, because most laboratories around the world (including the West) are dependent on disk testing and cannot test for MICs.
In 2000, typhoid fever caused an estimated 21.7 million illnesses and 217,000 deaths. It occurs most often in children and young adults between 5 and 19 years old. In 2013 it resulted in about 161,000 deaths – down from 181,000 in 1990. Infants, children, and adolescents in south-central and Southeast Asia experience the greatest burden of illness. Outbreaks of typhoid fever are also frequently reported from sub-Saharan Africa and countries in Southeast Asia. Historically, in the pre-antibiotic era, the case fatality rate of typhoid fever was 10–20%. Today, with prompt treatment, it is less than 1%. However, about 3–5% of individuals who are infected will develop a chronic infection in the gall bladder. Since S. Typhi is human-restricted, these chronic carriers become the crucial reservoir, which can persist for decades for further spread of the disease, further complicating the identification and treatment of the disease. Lately, the study of Typhi associated with a large outbreak and a carrier at the genome level provides new insights into the pathogenesis of the pathogen.
In industrialized nations, water sanitation and food handling improvements have reduced the number of cases. Developing nations, such as those found in parts of Asia and Africa, have the highest rates of typhoid fever. These areas have a lack of access to clean water, proper sanitation systems, and proper health care facilities. For these areas, such access to basic public health needs is not in the near future.
In 430 BC, a plague, which some believe to have been typhoid fever, killed one-third of the population of Athens, including their leader Pericles. Following this disaster, 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. The 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 typhoid fever the most likely cause. In 2006, a study detected DNA sequences similar to those of the bacterium responsible for typhoid fever in dental pulp extracted from a burial pit dated to the time of the outbreak.
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. The disease is most commonly transmitted through poor hygiene habits and public sanitation conditions; during the period in question related to Athens above, the whole population of Attica was besieged within the Long Walls and lived in tents.
During the American Civil War, 81,360 Union soldiers died of typhoid or dysentery, far more than died of battle wounds. In the late 19th century, the 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.
During the Spanish–American War, American troops were exposed to typhoid fever in stateside training camps and overseas, largely due to inadequate sanitation systems. The Surgeon General of the Army, George Miller Sternberg, suggested that the War Department create a Typhoid Fever Board. Major Walter Reed, Edward O. Shakespeare, and Victor C. Vaughan were appointed August 18, 1898, with Reed being designated the President of the Board. The Typhoid Board determined that during the war, more soldiers died from this disease than from yellow fever or from battle wounds. The Board promoted sanitary measures including latrine policy, disinfection, camp relocation, and water sterilization, but by far the most successful antityphoid method was vaccination, which became compulsory in June 1911 for all federal troops.
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 carrier in the United States to be identified and traced. She was a cook in New York who was closely associated with 53 cases and three deaths. Public health authorities told Mary to give up working as a cook or have her gall bladder removed, as she had a chronic infection that kept her active as a carrier of the disease. 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.
During the course of treatment of a typhoid outbreak in a local village in 1838, English country doctor William Budd realised the "poisons" involved in infectious diseases multiplied in the intestines of the sick, were present in their excretions, and could be transmitted to the healthy through their consumption of contaminated water. He proposed strict isolation or quarantine as a method for containing such outbreaks in the future. The medical and scientific communities did not identify the role of microorganisms in infectious disease until the work of Robert Koch and Louis Pasteur.
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 Salmonella enterica enterica, serovar Typhi.
The British bacteriologist Almroth Edward Wright first developed an effective typhoid vaccine at the Army Medical School in Netley, Hampshire. It was introduced in 1896 and used successfully by the British during the Boer War in South Africa. At that time, typhoid often killed more soldiers at war than were lost due to enemy combat. Wright further developed his vaccine at a newly opened research department at St Mary's Hospital Medical School in London from 1902, where he established a method for measuring protective substances (opsonin) in human blood.
Citing the example of the Second Boer War, during which many soldiers died from easily preventable diseases, Wright convinced the British Army that 10 million vaccine doses should be produced for the troops being sent to the Western Front, thereby saving up to half a million lives during World War I. The British Army was the only combatant at the outbreak of the war to have its troops fully immunized against the bacterium. For the first time, their casualties due to combat exceeded those from disease.
In 1909, Frederick F. Russell, a U.S. Army physician, adopted Wright's typhoid vaccine for use with the US Army, 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. In 1908, the chlorination of public drinking water was a significant step in the US in the control of typhoid fever. The first permanent disinfection of drinking water in the U.S. was made in 1908 to the Jersey City, New Jersey, water supply. Credit for the decision to build the chlorination system has been given to John L. Leal. The chlorination facility was designed by George W. Fuller.
In 1942 doctors introduced antibiotics in clinical practice, greatly reducing mortality. Today, the incidence of typhoid fever in developed countries is around five cases per million people per year.
The disease has been referred to by various names, often associated with symptoms, such as gastric fever, enteric fever, abdominal typhus, infantile remittant fever, slow fever, nervous fever, and pythogenic fever.
Resembling or characteristic of typhus
Austin Steward (1793 – February 15, 1869) was an African-American abolitionist and author. He was born a slave and escaped from Virginia at about age 21, settling in Rochester, New York, and then Canada. His autobiography, Twenty-Two Years a Slave, was published in 1857.Carl C. Jeremiassen
Carl C. Jeremiassen (Adopted Chinese name: 冶基善, 1847–1901) was a Danish sea captain. He is known today as the first Protestant missionary to Hainan island and the translator of portions of the Old and New Testament into the Hainanese language.Charles Zeitler
Charles W. Zeitler (August 1871 – 1903) was an American football player from South Bend, Indiana. Zeitler was the first quarterback for the University of Notre Dame to win four games.
Zeitler was born to a family of Bavarian immigrants in Clay Township, just north of South Bend, Indiana. His father, John V. Zeitler, was a very wealthy landowner and farmer who had held local office as a trustee and assessor.
Joining the Notre Dame football team in 1893 at a time when the program had just begun to schedule major opponents in earnest, Zeitler made the most of the opportunity, beginning the season 4-0 with victories over Kalamazoo, Albion, DeLasalle and Hillsdale, before finally falling 0-8 to Chicago in a road game on New Year's Day. The following season, Zeitler moved to the right end position, yielding the quarterback job to Nicholas Dinkel.
Zeitler returned to his homestead after graduation. In 1903 he died of typhoid fever. He is buried in the South Bend City Cemetery.Francis Burr
Francis Hardon Burr (September 15, 1886 – December 5, 1910) was an American football player. He was a first-team All-American guard in 1906 and captain of the 1908 Harvard Crimson football team. After he died of typhoid fever in 1910, the Francis H. Burr Award was established in his honor.Hepatitis A and typhoid vaccine
Hepatitis A and typhoid vaccine is a combination vaccine to protect against the infectious diseases hepatitis A and typhoid. It is a combination of inactivated Hepatitis A virus and Vi polysaccharide of Salmonella typhi bacteria. Branded formulations include Hepatyrix from GlaxoSmithKline, and ViVaxim and ViATIM from Sanofi Pasteur.Herb Alward
James Herbert Alward (November 1, 1865 – December 21, 1897) was an American football player and coach. He served as the third head football coach at the University of Wisconsin–Madison for a single season in 1891, compiling a record of 3–1–1. He died of typhoid fever in 1897.Alward would go on to coach for the Armour Institute (later merged into Illinois Institute of Technology) and Rush Medical College.Joe Nealon
James Joseph Nealon (December 15, 1884 – April 2, 1910) was a professional baseball player. He was born in Sacramento, California, and died in San Francisco, at the age of 25.
He was a first baseman over parts of 2 seasons (1906–1907) with the Pittsburgh Pirates. In his rookie season in 1906, he tied for the National League lead in RBIs with Harry Steinfeldt. The next year, he contracted tuberculosis, ending his baseball career. He subsequently died of typhoid pneumonia at the age of 25.Leland Stanford Jr.
Leland Stanford Jr. (May 14, 1868 – March 13, 1884), known as Leland DeWitt Stanford until age nine, is the namesake of Stanford University, adjacent to Palo Alto, California, United States.List of notifiable diseases
The following is a list of notifiable diseases arranged by country.Maganlal Gandhi
Maganlal Khushalchand Gandhi (1883–1928) was a follower of Mohandas Karamchand Gandhi. Grandson of an uncle of the Mahatma, he died of typhoid at Patna on 23 April 1928.
Maganlal Gandhi is cited in many works of Mohandas Gandhi. It is he who suggested the word Satyagraha to define Gandhi's nonviolence methods. According to Gandhi, Maganlal was the heart and soul of Sabarmati Ashram. He followed Gandhi in South Africa in 1903 "in the hope of making a bit of fortune", but instead followed his uncle's self-imposed poverty and joined the Phoenix Settlement.Mary Mallon
Mary Mallon (September 23, 1869 – November 11, 1938), also known as Typhoid Mary, was an Irish-American cook. She was the first person in the United States identified as an asymptomatic carrier of the pathogen associated with typhoid fever. She was presumed to have infected 51 people, three of whom died, over the course of her career as a cook. She was twice forcibly isolated by public health authorities and died after a total of nearly three decades in isolation.Paratyphoid fever
Paratyphoid fever, also known simply as paratyphoid, is a bacterial infection caused by one of the three types of Salmonella enterica. Symptoms usually begin 6–30 days after exposure and are the same as those of typhoid fever. Often, a gradual onset of a high fever occurs over several days. Weakness, loss of appetite, and headaches also commonly occur. Some people develop a skin rash with rose-colored spots. Without treatment, symptoms may last weeks or months. Other people may carry the bacteria without being affected; however, they are still able to spread the disease to others. Both typhoid and paratyphoid are of similar severity. Paratyphoid and typhoid fever are types of enteric fever.Paratyphoid is caused by the bacterium Salmonella enterica of the serotypes Paratyphi A, Paratyphi B, or Paratyphi C growing in the intestines and blood. They are usually spread by eating or drinking food or water contaminated with the feces of an infected person. They may occur when a person who prepares food is infected. Risk factors include poor sanitation as is found among poor crowded populations. Occasionally, they may be transmitted by sex. Humans are the only animals infected. Diagnosis may be based on symptoms and confirmed by either culturing the bacteria or detecting the bacterial DNA in the blood, stool, or bone marrow. Culturing the bacteria can be difficult. Bone-marrow testing is the most accurate. Symptoms are similar to that of many other infectious diseases. Typhus is an unrelated disease.While no vaccine is available specifically for paratyphoid, the typhoid vaccine may provide some benefit. Prevention includes drinking clean water, better sanitation, and better handwashing. Treatment of the disease is with antibiotics such as azithromycin. Resistance to a number of other previously effective antibiotics is common.Paratyphoid affects about six million people a year. It is most common in parts of Asia and rare in the developed world. Most cases are due to Paratyphi A rather than Paratyphi B or C. In 2015, paratyphoid fever resulted in about 29,200 deaths, down from 63,000 deaths in 1990. The risk of death is between 10 and 15% without treatment, while with treatment, it may be less than 1%.Reuben W. Stroud
Reuben W. Stroud (1841 in Lenox, Madison County, New York – December 2, 1875 in Syracuse, Onondaga County, New York) was an American civil engineer and politician from New York.Salmonella enterica
Salmonella enterica (formerly Salmonella choleraesuis) is a rod-shaped, flagellate, facultative aerobic, Gram-negative bacterium and a species of the genus Salmonella. A number of its serovars are serious human pathogens.Simon Brown (Massachusetts)
Simon Brown (November 29, 1802 – February 27, 1873) was an American politician who served as the 21st Lieutenant Governor for the Commonwealth of Massachusetts from 1855 to 1856. He was then an at-large delegate to the 1856 Republican Convention in Philadelphia where he supported the nomination of John C. Fremont. Professionally, Brown was a printer and publisher, including of the New England Farmer, working in Boston. He died at Concord, Massachusetts of typhoid fever, in 1873.Ty21a
Ty21a is a live attenuated bacterial vaccine that protects against typhoid. First licensed in Europe in 1983 and in the USA in 1989, it is an orally administered, live-attenuated Ty2 strain of S. Typhi in which multiple genes,
including the genes responsible for the production of Vi, have been mutated chemically so as to render it harmless but nevertheless immunogenic. It is one of two typhoid vaccines currently recommended by the World Health Organization (the other being the Vi capsular polysaccharide vaccine).The vaccine is given by mouth. The vaccine is presented either as enteric coated capsules or as a liquid suspension. The vaccine must be stored at 2 to 8 °C, but will retain its potency for 14 days at 25 °C.Vi capsular polysaccharide vaccine
Not to be confused with Ty21a. For an overview of vaccines against typhoid fever, see Typhoid vaccine.
The Vi capsular polysaccharide vaccine (or ViCPS) is one of two vaccines recommended by the World Health Organization for the prevention of typhoid (the other is Ty21a). The vaccine was first licensed in the US in 1994 and is made from the purified Vi capsular polysaccharide from the Ty2 Salmonella Typhi strain; it is a subunit vaccine. A newer conjugate form of the vaccine (Vi bound to a non-toxic recombinant Pseudomonas aeruginosa exotoxin, or Vi-rEPA) has enhanced efficacy, including protection of children under 5 years of age.Willard Louis
Willard Louis (April 19, 1882 – July 22, 1926) was an American stage and film actor of the silent era. He appeared in 81 films between 1911 and 1926. He was born in San Francisco, California, and died in Glendale, California from a combination of typhoid fever and pneumonia, aged 44.William Wallace Lincoln
William Wallace Lincoln (December 21, 1850 – February 20, 1862) was the third son of President Abraham Lincoln and Mary Todd Lincoln. He was named after Mary's brother-in-law Dr. William Wallace.