Typhoid fever

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Typhoid fever
Other names: Slow fever, typhoid
Rose spots on the chest of a person with typhoid fever
SpecialtyInfectious disease
SymptomsFever, abdominal pain, headache, rash[1]
Usual onset6–30 days after exposure[1][2]
CausesSalmonella enterica subsp. enterica (spread by food or water contaminated with feces)[3][4]
Risk factorsPoor sanitation, poor hygiene.[3]
Diagnostic methodBacterial culture, DNA detection[2][3][5]
Differential diagnosisOther infectious diseases[6]
PreventionTyphoid vaccine, handwashing[2][7]
Frequency12.5 million (2015)[8]
Deaths149,000 (2015)[9]

Typhoid fever, also known simply as typhoid, is a bacterial infection due to a specific type of Salmonella that causes symptoms.[3] Symptoms may vary from mild to severe, and usually begin 6 to 30 days after exposure.[1][2] Often there is a gradual onset of a high fever over several days.[1] This is commonly accompanied by weakness, abdominal pain, constipation, headaches, and mild vomiting.[2][6] Some people develop a skin rash with rose colored spots.[2] In severe cases, people may experience confusion.[6] Without treatment, symptoms may last weeks or months.[2] Diarrhea is uncommon.[6] Other people may carry the bacterium without being affected; however, they are still able to spread the disease to others.[4] Typhoid fever is a type of enteric fever, along with paratyphoid fever.[3]

The cause is the bacterium Salmonella enterica subsp. enterica serovar Typhi growing in the intestines and blood.[2][6] Typhoid is spread by eating or drinking food or water contaminated with the feces of an infected person.[4] Risk factors include poor sanitation and poor hygiene.[3] Those who travel in the developing world are also at risk.[6] Only humans can be infected.[4] Symptoms are similar to those of many other infectious diseases.[6] Diagnosis is by either culturing the bacteria or detecting their DNA in the blood, stool, or bone marrow.[2][3][5] Culturing the bacterium can be difficult.[10] Bone-marrow testing is the most accurate.[5]

A typhoid vaccine can prevent about 40 to 90% of cases during the first two years.[7] The vaccine may have some effect for up to seven years.[3] For those at high risk or people traveling to areas where the disease is common, vaccination is recommended.[4] Other efforts to prevent the disease include providing clean drinking water, good sanitation, and handwashing.[2][4] Until an individual's infection is confirmed as cleared, the individual should not prepare food for others.[2] The disease is treated with antibiotics such as azithromycin, fluoroquinolones, or third-generation cephalosporins.[3] Resistance to these antibiotics has been developing, which has made treatment of the disease more difficult.[3][11]

In 2015, 12.5 million new cases worldwide were reported.[8] The disease is most common in India.[3] Children are most commonly affected.[3][4] 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.[4] Each year in the United States, about 400 cases are reported and the disease occurs in an estimated 6,000 people.[6][12] In 2015, it resulted in about 149,000 deaths worldwide – down from 181,000 in 1990 (about 0.3% of the global total).[9][13] The risk of death may be as high as 20% without treatment.[4] With treatment, it is between 1 and 4%.[3][4] Typhus is a different disease.[14] However, the name typhoid means "resembling typhus" due to the similarity in symptoms.[15]

Signs and symptoms

Rose spots on chest of a person with typhoid fever

Classically, the progression 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.[16]

  • In the first week, the body temperature rises slowly, and fever fluctuations are seen with relative bradycardia (Faget sign), malaise, headache, and cough. A bloody nose (epistaxis) is seen in a quarter of cases, and abdominal pain is also possible. A decrease in the number of circulating white blood cells (leukopenia) occurs with eosinopenia and relative lymphocytosis; blood cultures are positive for Salmonella enterica subsp. enterica serovar Typhi. The Widal test is usually negative in the first week.[17]
  • In the second week, the person is often too tired to get up, with high fever in plateau around 40 °C (104 °F) and bradycardia (sphygmothermic dissociation or Faget sign), classically with a dicrotic pulse wave. Delirium can occur, where the patient is often calm, but sometimes becomes agitated. This delirium has led to typhoid receiving the nickname "nervous fever". Rose spots appear on the lower chest and abdomen in around a third of patients. Rhonchi (rattling breathing sounds) are heard in the base of the lungs. The abdomen is distended and painful in the right lower quadrant, where a rumbling sound can be heard. Diarrhea can occur in this stage, but constipation is also common. The spleen and liver are enlarged (hepatosplenomegaly) and tender, and liver transaminases are elevated. The Widal test is strongly positive, with antiO and antiH antibodies. Blood cultures are sometimes still positive at this stage.
  • In the third week of typhoid fever, a number of complications can occur:
    • Intestinal haemorrhage due to bleeding in congested Peyer's patches occurs; this can be very serious, but is usually not fatal.
    • Intestinal perforation in the distal ileum is a very serious complication and is frequently fatal. It may occur without alarming symptoms until septicaemia or diffuse peritonitis sets in.
    • Encephalitis
    • Respiratory diseases such as pneumonia and acute bronchitis
    • 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. Dehydration ensues, and the patient is delirious (typhoid state). One-third of affected individuals develop a macular rash on the trunk.
    • Low platelet count (thrombocytopenia) can sometimes be seen.[18]


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


The Gram-negative bacterium that causes typhoid fever is Salmonella enterica subsp. enterica serovar Typhi. Based on MLST subtyping scheme, the two main sequence types of the S. Typhi are ST1 and ST2, which are currently widespread globally.[19] The global phylogeographical analysis showed dominance of a haplotype 58 (H58) which probably originated in India during late 1980s and now spreading through the world carrying multidrug resistance.[20] A recently proposed and more detailed genotyping scheme has been reported in 2016 and is being used widely since. This scheme re-classified the nomemclature of H58 to genotype 4.3.1.[21]


Unlike other strains of Salmonella, no animal carriers of typhoid are known.[22] Humans are the only known carriers of the bacteria.[22] S. enterica subsp. enterica serovar Typhi is spread through the fecal-oral route from individuals who are currently infected and from asymptomatic carriers of the bacteria.[22] An asymptomatic human carrier is an individual who is still excreting typhoid bacteria in their stool a year after the acute stage of the infection.[22]


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.[23]

Widal test

widal test card

Widal test is used to identify specific antibodies in serum of people with typhoid by using antigen-antibody interactions.

In this test, the serum is mixed with a dead bacterial suspension of salmonella having specific antigens on it. If the patient's serum is carrying antibodies against those antigens then they get attached to them forming clumping which indicated the positivity of the test. If clumping does not occur then the test is negative. 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.[24]

Rapid diagnostic tests

Rapid diagnostic tests such as Tubex, Typhidot, and Test-It has shown moderate diagnostic accuracy.[25]


The test is based on the presence of specific IgM and IgG antibodies to a specific 50Kd OMP antigen. This test is carried out on a cellulose nitrate membrane where a specific S. typhi outer membrane protein is attached as fixed test lines. It separately identifies IgM and IgG antibodies. IgM shows recent infection whereas IgG signifies remote infection.

The sample pad of this kit contains colloidal gold-anti-human IgG or gold-anti-human IgM. If the sample contains IgG and IgM antibodies against those antigens then they will react and get turned into red color. This complex will continue to move forward and the IgG and IgM antibodies will get attached to the first test line where IgG and IgM antigens are present giving a pink-purplish colored band. This complex will continue to move further and reach the control line which consists of rabbit anti-mouse antibody which bends the mouse anti-human IgG or IgM antibodies. The main purpose of the control line is to indicate a proper migration and reagent color. The typhidot test becomes positive within 2–3 days of infection.

Two colored bands indicate a positive test. Single-band of control line indicates a negative test. Single-band of first fixed line or no bands at all indicates invalid tests. The most important limitation of this test is that it is not quantitative and the result is only positive or negative.[26]

Tubex test

Tubex test contains two types of particles brown magnetic particles coated with antigen and blue indicator particles coated with O9 antibody. During the test, if antibodies are present in the serum then they will get attached to the brown magnetic particles and settle down at the base and the blue indicator particles remain up in the solution giving a blue color that indicates positivity of the test.

If the serum does not have an antibody in it then the blue particle gets attached to the brown particles and settled down at the bottom giving no color to the solution which means the test is negative and they do not have typhoid.[27]


Doctor administering a typhoid vaccination at a school in San Augustine County, Texas, 1943

Sanitation and hygiene are important to prevent typhoid. It 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 public streets, which led to large number of flies,[28] which are known as vectors of many pathogens, including Salmonella spp.[29] According to statistics from the United States Centers for Disease Control and Prevention, the chlorination of drinking water has led to dramatic decreases in the transmission of typhoid fever in the United States.[30]


Two typhoid vaccines are licensed for use for the prevention of typhoid:[7] 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.[7] 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).[31]

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.[32] Although vaccination programs for typhoid have proven to be effective, they alone cannot eliminate typhoid fever.[32] Combining the use of vaccines with increasing public health efforts is the only proven way to control this disease.[32]

Since the 1990s, two typhoid fever vaccines have been recommended by the WHO. The ViPS vaccine is given via injection, while the Ty21a is taken through capsules. Only people 2 years or older are recommended to be vaccinated with the ViPS vaccine, and it 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.[32]

A version combined with hepatitis A is also available.[33]

Results of a phase 3 trial of typhoid conjugate vaccine (TCV) in December 2019 reported 81% fewer cases among children.[34][35]


Drinking fluids

The rediscovery of oral rehydration therapy in the 1960s provided a simple way to prevent many of the deaths of diarrheal diseases in general.[36]


Where resistance is uncommon, the treatment of choice is a fluoroquinolone such as ciprofloxacin.[37][38] Otherwise, a third-generation cephalosporin such as ceftriaxone or cefotaxime is the first choice.[39][40][41][42] Cefixime is a suitable oral alternative.[43][44]

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.[45] Treatment of the disease with antibiotics reduces the case-fatality rate to about 1%.[46]

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.[47]


Surgery is usually indicated if intestinal perforation occurs. One study found a 30-day mortality rate of 9% (8/88), and surgical site infections at 67% (59/88), with the disease burden borne predominantly by low-resource countries.[48]

For surgical treatment, 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 sometimes successful, especially in patients with gallstones, but is not always successful in eradicating the carrier state because of persisting liver infection.[49][50]


As resistance to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, and streptomycin is now common, these agents are no longer used as first–line treatment of typhoid fever.[51] Typhoid resistant to these agents is known as multidrug-resistant typhoid.[52]

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 resistant typhoid in populations than both fluoroquinolone drugs and ceftriaxone.[38] Azithromycin can be taken by mouth and is less expensive than ceftriaxone which is given by injection.[53]

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 fluoroquinolones, the class which CIP belongs, (MIC 0.125–1.0 mg/l) would not be picked up by this method.[54]


        Incidence of typhoid fever
   Strongly endemic
   Sporadic cases

In 2000, typhoid fever caused an estimated 21.7 million illnesses and 217,000 deaths.[5] It occurs most often in children and young adults between 5 and 19 years old.[55] In 2013, it resulted in about 161,000 deaths – down from 181,000 in 1990.[13] Infants, children, and adolescents in south-central and Southeast Asia experience the greatest burden of illness.[56] Outbreaks of typhoid fever are also frequently reported from sub-Saharan Africa and countries in Southeast Asia.[57][58][59] In the United States, about 400 cases occur each year, and 75% of these are acquired while traveling internationally.[60][61]

Historically, before the antibiotic era, the case fatality rate of typhoid fever was 10–20%. Today, with prompt treatment, it is less than 1%.[62] However, about 3–5% of individuals who are infected develop a chronic infection in the gall bladder.[63] Since S. enterica subsp. enterica serovar 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.[64] Lately, the study of S. enterica subsp. enterica serovar Typhi associated with a large outbreak and a carrier at the genome level provides new insights into the pathogenesis of the pathogen.[65][66]

In industrialized nations, water sanitation and food handling improvements have reduced the number of cases.[67] 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.[68]

In 2004–2005 an outbreak in the Democratic Republic of Congo resulted in more than 42,000 cases and 214 deaths.[55] Since November 2016, Pakistan has had an outbreak of extensively drug-resistant (XDR) typhoid fever.[69]



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.[70] He proposed strict isolation or quarantine as a method for containing such outbreaks in the future.[71] The medical and scientific communities did not identify the role of microorganisms in infectious disease until the work of Robert Koch and Louis Pasteur.[72][73][74]

Organism involved

Almroth Edward Wright developed the first effective typhoid vaccine.

In 1880, Karl Joseph Eberth described a bacillus that he suspected was the cause of typhoid.[75][76][77] In 1884, pathologist Georg Theodor August Gaffky (1850–1918) confirmed Eberth's findings,[78] 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.[79]


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.[80] 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.[81]

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.[82] 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.[83]

In 1909, Frederick F. Russell, a U.S. Army physician, adopted Wright's typhoid vaccine for use with the 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.[84]

Chlorination of water

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).

Most developed countries had declining rates of typhoid fever throughout the first half of the 20th century due to vaccinations and advances in public sanitation and hygiene. In 1893 attempts were made to chlorinate the water supply in Hamburg, Germany and in 1897 Maidstone, England was the first town to have its entire water supply chlorinated.[85] In 1905, following an outbreak of typhoid fever, the City of Lincoln, England instituted permanent water chlorination.[86] The first permanent disinfection of drinking water in the US 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.[87] The chlorination facility was designed by George W. Fuller.[88]

20th century

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.

In 1902, guests at mayoral banquets in Southampton and Winchester, England, became ill and four died, including the Dean of Winchester, after consuming oysters. The infection was due to oysters sourced from Emsworth, where the oyster beds had been contaminated with raw sewage.[89][90]

The most notorious carrier of typhoid fever, but by no means the most destructive, was Mary Mallon, 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 associated with 53 cases and three deaths.[91]


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, pythogenic fever,[92] drain fever and low fever.[93]

Notable cases

See also


  1. 1.0 1.1 1.2 1.3 Newton, Anna E. (2014). "3 Infectious Diseases Related To Travel". CDC health information for international travel 2014 : the yellow book. ISBN 9780199948499. Archived from the original on 2015-07-02.
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 "Typhoid Fever". cdc.gov. May 14, 2013. Archived from the original on 6 June 2016. Retrieved 28 March 2015.
  3. 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 Wain J, Hendriksen RS, Mikoleit ML, Keddy KH, Ochiai RL (March 2015). "Typhoid fever". Lancet. 385 (9973): 1136–45. doi:10.1016/s0140-6736(13)62708-7. PMID 25458731. S2CID 2409150.
  4. 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 4.9 "Typhoid vaccines: WHO position paper" (PDF). Releve Epidemiologique Hebdomadaire. 83 (6): 49–59. February 2008. PMID 18260212. Archived (PDF) from the original on April 2, 2015.
  5. 5.0 5.1 5.2 5.3 Crump JA, Mintz ED (January 2010). "Global trends in typhoid and paratyphoid Fever". Clinical Infectious Diseases. 50 (2): 241–6. doi:10.1086/649541. PMC 2798017. PMID 20014951.
  6. 6.0 6.1 6.2 6.3 6.4 6.5 6.6 6.7 "Typhoid Fever". cdc.gov. May 14, 2013. Archived from the original on 2 April 2015. Retrieved 28 March 2015.
  7. 7.0 7.1 7.2 7.3 Milligan R, Paul M, Richardson M, Neuberger A (May 2018). "Vaccines for preventing typhoid fever". The Cochrane Database of Systematic Reviews. 5: CD001261. doi:10.1002/14651858.CD001261.pub4. PMC 6494485. PMID 29851031.
  8. 8.0 8.1 Vos T, Allen C, Arora M, Barber RM, Bhutta ZA, Brown A, et al. (GBD 2015 Disease and Injury Incidence and Prevalence Collaborators) (October 2016). "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1545–1602. doi:10.1016/S0140-6736(16)31678-6. PMC 5055577. PMID 27733282.
  9. 9.0 9.1 Wang H, Naghavi M, Allen C, Barber RM, Bhutta ZA, Carter A, et al. (GBD 2015 Mortality and Causes of Death Collaborators) (October 2016). "Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1459–1544. doi:10.1016/s0140-6736(16)31012-1. PMC 5388903. PMID 27733281.
  10. Magill, Alan J. (2013). Hunter's tropical medicine and emerging infectious diseases (9th ed.). London: Saunders/Elsevier. pp. 568–572. ISBN 9781455740437. Archived from the original on 2017-02-28.
  11. Chatham-Stephens K, Medalla F, Hughes M, Appiah GD, Aubert RD, Caidi H, et al. (January 2019). "Emergence of Extensively Drug-Resistant Salmonella Typhi Infections Among Travelers to or from Pakistan - United States, 2016-2018". MMWR. Morbidity and Mortality Weekly Report. 68 (1): 11–13. doi:10.15585/mmwr.mm6801a3. PMC 6342547. PMID 30629573.
  12. Jackson BR, Iqbal S, Mahon B (March 2015). "Updated recommendations for the use of typhoid vaccine--Advisory Committee on Immunization Practices, United States, 2015". MMWR. Morbidity and Mortality Weekly Report. 64 (11): 305–8. PMC 4584884. PMID 25811680.
  13. 13.0 13.1 Abubakar II, Tillmann T, Banerjee A, et al. (GBD 2013 Mortality and Causes of Death Collaborators) (January 2015). "Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013". Lancet. 385 (9963): 117–71. doi:10.1016/S0140-6736(14)61682-2. PMC 4340604. PMID 25530442.
  14. Cunha BA (March 2004). "Osler on typhoid fever: differentiating typhoid from typhus and malaria". Infectious Disease Clinics of North America. 18 (1): 111–25. doi:10.1016/S0891-5520(03)00094-1. PMID 15081508.
  15. "Oxford English Dictionary (Online)". p. typhoid, adj. and n. Archived from the original on 11 January 2008. Retrieved 28 March 2015. Resembling or characteristic of typhus
  16. "Typhoid". Merriam Webster Dictionary. Archived from the original on 2013-07-02. Retrieved 2013-06-24.
  17. Kumar P, Kumar R (March 2017). "Enteric Fever". Indian Journal of Pediatrics. 84 (3): 227–230. doi:10.1007/s12098-016-2246-4. PMID 27796818. S2CID 3825885.
  18. "Typhoid fever: MedlinePlus Medical Encyclopedia". medlineplus.gov. Archived from the original on 2020-04-13. Retrieved 2020-04-21.
  19. Yap KP, Ho WS, Gan HM, Chai LC, Thong KL (2016). "Global MLST of Salmonella Typhi Revisited in Post-genomic Era: Genetic Conservation, Population Structure, and Comparative Genomics of Rare Sequence Types". Frontiers in Microbiology. 7: 270. doi:10.3389/fmicb.2016.00270. PMC 4774407. PMID 26973639.
  20. Wong VK, Baker S, Pickard DJ, Parkhill J, Page AJ, Feasey NA, et al. (June 2015). "Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events". Nature Genetics. 47 (6): 632–9. doi:10.1038/ng.3281. PMC 4921243. PMID 25961941.
  21. Wong VK, Baker S, Connor TR, Pickard D, Page AJ, Dave J, et al. (October 2016). "An extended genotyping framework for Salmonella enterica serovar Typhi, the cause of human typhoid". Nature Communications. 7 (1): 12827. Bibcode:2016NatCo...712827W. doi:10.1038/ncomms12827. PMC 5059462. PMID 27703135.
  22. 22.0 22.1 22.2 22.3 Eng SK, Pusparajah P, Ab Mutalib NS, Ser HL, Chan KG, Lee LH (June 2015). "Salmonella:A review on pathogenesis, epidemiology and antibiotic resistance". Frontiers in Life Science. 8 (3): 284–293. doi:10.1080/21553769.2015.1051243.
  23. Ryan KJ, Ray CG, eds. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. ISBN 978-0-8385-8529-0.
  24. Feasey NA, Gordon MA (2014). "Salmonella Infections". In Farrar J, Hotez P, Junghanss T, Kang G, Lalloo D, White NJ (eds.). Manson's Tropical Infectious Diseases (23rd ed.). Saunders Ltd. doi:10.1016/B978-0-7020-5101-2.00026-1.
  25. Wijedoru L, Mallett S, Parry CM, et al. (Cochrane Infectious Diseases Group) (May 2017). "Rapid diagnostic tests for typhoid and paratyphoid (enteric) fever". The Cochrane Database of Systematic Reviews. 5: CD008892. doi:10.1002/14651858.CD008892.pub2. PMC 5458098. PMID 28545155.
  26. Lim PL, Tam FC, Cheong YM, Jegathesan M (August 1998). "One-step 2-minute test to detect typhoid-specific antibodies based on particle separation in tubes". Journal of Clinical Microbiology. 36 (8): 2271–8. doi:10.1128/JCM.36.8.2271-2278.1998. PMC 105030. PMID 9666004.
  27. "TYPHIDOT Rapid IgG/IgM (Combo)" (PDF). Reszon Diagnostics International. Archived (PDF) from the original on 13 February 2020. Retrieved 14 November 2019.
  28. "The Great Horse Manure Crisis of 1894". Archived from the original on 2015-05-25.
  29. Cirillo VJ (2006). ""Winged sponges": houseflies as carriers of typhoid fever in 19th- and early 20th-century military camps". Perspectives in Biology and Medicine. 49 (1): 52–63. doi:10.1353/pbm.2006.0005. PMID 16489276. S2CID 41428479.
  30. "History of Drinking Water Treatment | Drinking Water | Healthy Water | CDC". www.cdc.gov. 2018-10-10. Archived from the original on 2020-04-02. Retrieved 2020-04-21.
  31. Marathe SA, Lahiri A, Negi VD, Chakravortty D (2012). "Typhoid fever & vaccine development: a partially answered question". The Indian Journal of Medical Research. 135 (2): 161–9. PMC 3336846. PMID 22446857.
  32. 32.0 32.1 32.2 32.3 Date KA, Bentsi-Enchill A, Marks F, Fox K (June 2015). "Typhoid fever vaccination strategies". Vaccine. 33 Suppl 3: C55-61. doi:10.1016/j.vaccine.2015.04.028. PMID 25902360.
  33. "Vivaxim Solution for injection". NPS MedicineWise. Archived from the original on 1 October 2015. Retrieved 10 April 2017.
  34. Gallagher, James (4 December 2019). "Typhoid vaccine 'works fantastically well'". BBC News. Archived from the original on 21 January 2020. Retrieved 17 January 2020.
  35. Shakya M, Colin-Jones R, Theiss-Nyland K, Voysey M, Pant D, Smith N, et al. (December 2019). "Phase 3 Efficacy Analysis of a Typhoid Conjugate Vaccine Trial in Nepal". The New England Journal of Medicine. 381 (23): 2209–2218. doi:10.1056/NEJMoa1905047. PMC 6785806. PMID 31800986.
  36. "UpToDate". www.uptodate.com. Archived from the original on 2020-08-09. Retrieved 2020-04-21.
  37. Parry CM, Beeching NJ (June 2009). "Treatment of enteric fever". BMJ. 338: b1159. doi:10.1136/bmj.b1159. PMID 19493937. S2CID 3264721.
  38. 38.0 38.1 Effa EE, Lassi ZS, Critchley JA, Garner P, Sinclair D, Olliaro PL, Bhutta ZA (October 2011). "Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever)". The Cochrane Database of Systematic Reviews (10): CD004530. doi:10.1002/14651858.CD004530.pub4. PMC 6532575. PMID 21975746. Archived from the original on 2020-04-16. Retrieved 2020-08-06.
  39. Soe GB, Overturf GD (1987). "Treatment of typhoid fever and other systemic salmonelloses with cefotaxime, ceftriaxone, cefoperazone, and other newer cephalosporins". Reviews of Infectious Diseases. 9 (4): 719–36. doi:10.1093/clinids/9.4.719. JSTOR 4454162. PMID 3125577.
  40. Wallace MR, Yousif AA, Mahroos GA, Mapes T, Threlfall EJ, Rowe B, Hyams KC (December 1993). "Ciprofloxacin versus ceftriaxone in the treatment of multiresistant typhoid fever". European Journal of Clinical Microbiology & Infectious Diseases. 12 (12): 907–10. doi:10.1007/BF01992163. PMID 8187784. Archived from the original on 2020-08-09. Retrieved 2020-08-06.
  41. Dutta P, Mitra U, Dutta S, De A, Chatterjee MK, Bhattacharya SK (June 2001). "Ceftriaxone therapy in ciprofloxacin treatment failure typhoid fever in children". The Indian Journal of Medical Research. 113: 210–3. PMID 11816954.
  42. Коваленко АН, et al. (2011). "Особенности клиники, диагностики и лечения брюшного тифа у лиц молодого возраста". Voen.-meditsinskii Zhurnal. 332 (1): 33–39.
  43. Bhutta ZA, Khan IA, Molla AM (November 1994). "Therapy of multidrug-resistant typhoid fever with oral cefixime vs. intravenous ceftriaxone". The Pediatric Infectious Disease Journal. 13 (11): 990–4. doi:10.1097/00006454-199411000-00010. PMID 7845753.
  44. Cao XT, Kneen R, Nguyen TA, Truong DL, White NJ, Parry CM (March 1999). "A comparative study of ofloxacin and cefixime for treatment of typhoid fever in children. The Dong Nai Pediatric Center Typhoid Study Group". The Pediatric Infectious Disease Journal. 18 (3): 245–8. doi:10.1097/00006454-199903000-00007. PMID 10093945.
  45. Baron S et al.
  46. "Diarrhoeal Diseases (Updated February 2009)". Archived from the original on November 2, 2011. Retrieved 2013-04-25.. World Health Organization
  47. "WHO | Typhoid fever". www.who.int. Archived from the original on 2017-07-27. Retrieved 2017-08-10.
  48. Anyomih TK, Drake TM, Glasbey J, Fitzgerald JE, Ots R, et al. (GlobalSurg Collaborative) (October 2018). "Management and Outcomes Following Surgery for Gastrointestinal Typhoid: An International, Prospective, Multicentre Cohort Study". World Journal of Surgery. 42 (10): 3179–3188. doi:10.1007/s00268-018-4624-8. PMC 6132852. PMID 29725797.
  49. Waddington CS, Darton TC, Pollard AJ (January 2014). "The challenge of enteric fever". The Journal of Infection. Hot Topics in Infection and Immunity in Children - Papers from the 10th annual IIC meeting, Oxford, UK, 2012. 68 Suppl 1: S38-50. doi:10.1016/j.jinf.2013.09.013. PMID 24119827. Archived from the original on 2021-08-27. Retrieved 2020-08-06.
  50. Gonzalez-Escobedo G, Marshall JM, Gunn JS (January 2011). "Chronic and acute infection of the gall bladder by Salmonella Typhi: understanding the carrier state". Nature Reviews. Microbiology. 9 (1): 9–14. doi:10.1038/nrmicro2490. PMC 3255095. PMID 21113180.
  51. "Extensively Drug-Resistant Typhoid Fever in Pakistan - Watch - Level 1, Practice Usual Precautions - Travel Health Notices | Travelers' Health | CDC". wwwnc.cdc.gov. Archived from the original on 2020-12-15. Retrieved 2020-04-21.
  52. Zaki SA, Karande S (May 2011). "Multidrug-resistant typhoid fever: a review". Journal of Infection in Developing Countries. 5 (5): 324–37. doi:10.3855/jidc.1405. PMID 21628808.
  53. Gibani MM, Britto C, Pollard AJ (October 2018). "Typhoid and paratyphoid fever: a call to action". Current Opinion in Infectious Diseases. 31 (5): 440–448. doi:10.1097/QCO.0000000000000479. PMC 6319573. PMID 30138141.
  54. Cooke FJ, Wain J, Threlfall EJ (August 2006). "Fluoroquinolone resistance in Salmonella Typhi". BMJ. 333 (7563): 353–4. doi:10.1136/bmj.333.7563.353-b. PMC 1539082. PMID 16902221.
  55. 55.0 55.1 "Typhoid Fever". World Health Organization. Archived from the original on 2011-11-02. Retrieved 2007-08-28.
  56. Crump JA, Luby SP, Mintz ED (May 2004). "The global burden of typhoid fever". Bulletin of the World Health Organization. 82 (5): 346–53. PMC 2622843. PMID 15298225.
  57. Muyembe-Tamfum JJ, Veyi J, Kaswa M, Lunguya O, Verhaegen J, Boelaert M (January 2009). "An outbreak of peritonitis caused by multidrug-resistant Salmonella Typhi in Kinshasa, Democratic Republic of Congo". Travel Medicine and Infectious Disease. 7 (1): 40–3. doi:10.1016/j.tmaid.2008.12.006. PMID 19174300.
  58. Baddam R, Kumar N, Thong KL, Ngoi ST, Teh CS, Yap KP, et al. (July 2012). "Genetic fine structure of a Salmonella enterica serovar Typhi strain associated with the 2005 outbreak of typhoid fever in Kelantan, Malaysia". Journal of Bacteriology. 194 (13): 3565–6. doi:10.1128/jb.00581-12. PMC 3434757. PMID 22689247.
  59. Yap KP, Teh CS, Baddam R, Chai LC, Kumar N, Avasthi TS, et al. (September 2012). "Insights from the genome sequence of a Salmonella enterica serovar Typhi strain associated with a sporadic case of typhoid fever in Malaysia". Journal of Bacteriology. 194 (18): 5124–5. doi:10.1128/jb.01062-12. PMC 3430317. PMID 22933756.
  60. Matano LM, Morris HG, Wood BM, Meredith TC, Walker S (December 2016). "Accelerating the discovery of antibacterial compounds using pathway-directed whole cell screening". Bioorganic & Medicinal Chemistry. 24 (24): 6307–6314. doi:10.1016/j.bmc.2016.08.003. PMC 5180449. PMID 27594549.
  61. "Typhoid Fever" (PDF). Florida Department of Health. December 23, 2013. Archived (PDF) from the original on August 9, 2020. Retrieved August 6, 2020.
  62. Heymann, David L., ed. (2008), Control of Communicable Diseases Manual, Washington, D.C.: American Public Health Association, pg 665. ISBN 978-0-87553-189-2.
  63. Levine MM, Black RE, Lanata C (December 1982). "Precise estimation of the numbers of chronic carriers of Salmonella typhi in Santiago, Chile, an endemic area". The Journal of Infectious Diseases. 146 (6): 724–6. doi:10.1093/infdis/146.6.724. PMID 7142746.
  64. Gonzalez-Escobedo G, Marshall JM, Gunn JS (January 2011). "Chronic and acute infection of the gall bladder by Salmonella Typhi: understanding the carrier state". Nature Reviews. Microbiology. 9 (1): 9–14. doi:10.1038/nrmicro2490. PMC 3255095. PMID 21113180.
  65. Yap KP, Gan HM, Teh CS, Baddam R, Chai LC, Kumar N, et al. (November 2012). "Genome sequence and comparative pathogenomics analysis of a Salmonella enterica Serovar Typhi strain associated with a typhoid carrier in Malaysia". Journal of Bacteriology. 194 (21): 5970–1. doi:10.1128/jb.01416-12. PMC 3486090. PMID 23045488.
  66. Yap KP, Gan HM, Teh CS, Chai LC, Thong KL (November 2014). "Comparative genomics of closely related Salmonella enterica serovar Typhi strains reveals genome dynamics and the acquisition of novel pathogenic elements". BMC Genomics. 15 (1): 1007. doi:10.1186/1471-2164-15-1007. PMC 4289253. PMID 25412680.
  67. Crump JA, Sjölund-Karlsson M, Gordon MA, Parry CM (October 2015). "Epidemiology, Clinical Presentation, Laboratory Diagnosis, Antimicrobial Resistance, and Antimicrobial Management of Invasive Salmonella Infections". Clinical Microbiology Reviews. 28 (4): 901–37. doi:10.1128/CMR.00002-15. PMC 4503790. PMID 26180063.
  68. Khan MI, Pach A, Khan GM, Bajracharya D, Sahastrabuddhe S, Bhutta W, et al. (June 2015). "Typhoid vaccine introduction: An evidence-based pilot implementation project in Nepal and Pakistan". Vaccine. 33 Suppl 3: C62-7. doi:10.1016/j.vaccine.2015.03.087. PMID 25937612.
  69. "Extensively Drug-Resistant Typhoid Fever in Pakistan". Centers for Disease Control and Prevention. 30 September 2019. Archived from the original on 15 December 2020. Retrieved 6 August 2020.
  70. Asimov, Asimov's Biographical Encyclopedia of Science and Technology 2nd Revised edition
  71. Aronson SM (November 1995). "William Budd and typhoid fever". Rhode Island Medicine. 78 (11): 310. PMID 8547718.
  72. Tyndall, John (1886). "Introduction". In Vallery-Radot, René (ed.). Louis Pasteur: His Life and Labours. Translated by Lady Claud, Hamilton. NY: Appleton. p. 16. Archived from the original on 2020-08-19. Retrieved 2020-08-06.
  73. Whipham, Thomas T. (4 October 1902). "The Power of Observation in Medicine". Lancet: 912. Archived from the original on 20 August 2020. Retrieved 6 August 2020.
  74. Dolman, Claude Ernest; Wolfe, Richard J. (2003). Suppressing the Diseases of Animals and Man: Theobald Smith, Microbiologist. Boston Medical Library. p. 73. ISBN 9780674012202. Archived from the original on 2020-08-20. Retrieved 2020-08-06.
  75. Eberth CJ (1880). "Die Organismen in den Organen bei Typhus abdominalis" [Organisms in the [internal] organs in cases of Typhus abdominalis]. Archiv für pathologische Anatomie und Physiologie (in German). 81: 58–74. Archived from the original on 2021-02-27. Retrieved 2020-08-06.{{cite journal}}: CS1 maint: unrecognized language (link)
  76. Eberth CJ (1881). "Neue Untersuchungen über den Bacillus des Abdominaltyphus" [New investigations into the bacilli of abdominal typhoid]. Archiv für pathologische Anatomie und Physiologie (in German). 83: 486–501. Archived from the original on 2021-02-24. Retrieved 2020-08-06.{{cite journal}}: CS1 maint: unrecognized language (link)
  77. Eberth's findings were verified by Robert Koch Koch, Robert (1881). "Zur Untersuchung von pathogenen Organismen" [On the investigation of pathogenic organisms]. Mitteilungen aus dem Kaiserlichen Gesundheitsamte (in German). 1: 1–49. Archived from the original on 2017-04-23.{{cite journal}}: CS1 maint: unrecognized language (link)
  78. Gaffky G (1884). "Zur aetiologie des abdominaltyphus" [On the etiology of abdominal typhus]. Mitteillungen aus dem Kaiserlichen Gesundheitsamt (in German). 2: 372–420. Archived from the original on 2017-04-23.{{cite journal}}: CS1 maint: unrecognized language (link)
  79. Wertheim, Heiman F. L.; Horby, Peter; Woodall, John P. (2012). Atlas of Human Infectious Diseases (1st ed.). New York, NY: John Wiley & Sons. ISBN 978-1-4443-5467-6. OCLC 897547171.
  80. "Sir Almroth Edward Wright". Encyclopædia Britannica. Archived from the original on 2013-11-11.
  81. Wright AE, Douglas SR (1904-01-31). "An experimental investigation of the rôle of the blood fluids in connection with phagocytosis". Proceedings of the Royal Society of London. 72 (477–486): 357–370. doi:10.1098/rspl.1903.0062. ISSN 0370-1662.
  82. "Library and Archive Catalogue". Royal Society. Retrieved 1 November 2010.[permanent dead link]
  83. "Medical lessons from World War I underscore need to keep developing antimicrobial drugs". MinnPost. 2014-11-11. Archived from the original on 30 January 2016. Retrieved 8 September 2017.
  84. USAMRMC: 50 Years of Dedication to the Warfighter 1958–2008 (PDF). U.S. Army Medical Research & Material Command (2008). 2008. p. 5. ASIN B003WYKJNY. Archived from the original (PDF) on 2013-02-14. Retrieved 2013-03-27.
  85. "Typhoid Epidemic at Maidstone". Journal of the Sanitary Institute. 18: 388. October 1897.
  86. "A miracle for public health?". Archived from the original on 2014-01-09. Retrieved 2012-12-17.
  87. Leal, John L. (1909). "The Sterilization Plant of the Jersey City Water Supply Company at Boonton, N.J.". Proceedings American Water Works Association. pp. 100–9.
  88. Fuller, George W. (1909). "Description of the Process and Plant of the Jersey City Water Supply Company for the Sterilization of the Water of the Boonton Reservoir.". Proceedings American Water Works Association. pp. 110–34.
  89. "Emsworth Oysters". Emsworth Business Association. 10 February 2019. Archived from the original on 3 February 2016.
  90. Bulstrode, H. Timbrell (1903). "Dr. H. Timbrell Bulstrode's report to the Local Government Board upon alleged oyster-borne enteric fever and other illness following the mayoral banquets at Winchester and Southampton, and upon enteric fever occurring simultaneously elsewhere and also ascribed to oysters". London: HMSO: 1. Archived from the original on 7 July 2019. {{cite journal}}: Cite journal requires |journal= (help)
  91. "Nova: The Most Dangerous Woman in America". Archived from the original on 2010-04-26.
  92. "Typhoid Fever". Center for Emerging and Re-emerging Infectious Diseases. University of Washington. Archived from the original on 2019-12-08. Retrieved 2019-12-08.
  93. "TYPHOID OR DRAIN FEVER, AND HOW TO PREVENT ITS SPREADING". The Warwick Examiner and Times. 6 April 1878. Archived from the original on 9 August 2020. Retrieved 13 April 2020.
  94. Dennis, Brady (2011-09-29). "Willie Lincoln's death: A private agony for a president facing a nation of pain". The Washington Post. ISSN 0190-8286. Archived from the original on 2017-04-01. Retrieved 2017-03-12.
  95. Matthew HC (September 2004). "Edward VII (1841–1910)". Oxford Dictionary of National Biography. Oxford University Press (published May 2006). doi:10.1093/ref:odnb/32975. Archived from the original on 2016-03-02. (subscription or UK public library membership required)
  96. Paulley JW (December 1993). "The death of Albert Prince Consort: the case against typhoid fever". The Quarterly Journal of Medicine. 86 (12): 837–41. doi:10.1093/oxfordjournals.qjmed.a068768. PMID 8108541. Archived from the original on 2015-12-08.
  97. "A History of Stanford". Stanford University. Archived from the original on 10 March 2021. Retrieved 4 July 2018.
  98. Ruggles, Eleanor (1944). Gerard Manley Hopkins: A Life. Norton.
  99. Scott, Belinda F. (23 September 1910). "Scott, Henry James Herbert (1858–1910)". Biography – Henry James Herbert Scott. Australian Dictionary of Biography. National Centre of Biography, Australian National University. Archived from the original on 2011-02-21.
  100. "Straw for Silence". The Spectator. Vol. 203. F.C. Westley. 1959. ISSN 0038-6952. OCLC 1766325. Archived from the original on March 8, 2021. Retrieved March 16, 2011.
  101. Hakaru Hashimoto#Biography

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