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Typhoid Fever Workup

  • Author: John L Brusch, MD, FACP; Chief Editor: Michael Stuart Bronze, MD  more...
Updated: Feb 16, 2016

Laboratory Studies

The diagnosis of typhoid fever (enteric fever) is primarily clinical.

Importantly, the reported sensitivities of tests for S typhi vary greatly in the literature, even among the most recent articles and respected journals.


The criterion standard for diagnosis of typhoid fever has long been culture isolation of the organism. Cultures are widely considered 100% specific.

Culture of bone marrow aspirate is 90% sensitive until at least 5 days after commencement of antibiotics. However, this technique is extremely painful, which may outweigh its benefit.[36]

Blood, intestinal secretions (vomitus or duodenal aspirate), and stool culture results are positive for S typhi in approximately 85%-90% of patients with typhoid fever who present within the first week of onset. They decline to 20%-30% later in the disease course. In particular, stool culture may be positive for S typhi several days after ingestion of the bacteria secondary to inflammation of the intraluminal dendritic cells. Later in the illness, stool culture results are positive because of bacteria shed through the gallbladder.

Multiple blood cultures (>3) yield a sensitivity of 73%-97%. Large-volume (10-30 mL) blood culture and clot culture may increase the likelihood of detection.[37]

Stool culture alone yields a sensitivity of less than 50%, and urine culture alone is even less sensitive. Cultures of punch-biopsy samples of rose spots reportedly yield a sensitivity of 63% and may show positive results even after administration of antibiotics. A single rectal swab culture upon hospital admission can be expected to detect S typhi in 30%-40% of patients. S typhi has also been isolated from the cerebrospinal fluid, peritoneal fluid, mesenteric lymph nodes, resected intestine, pharynx, tonsils, abscess, and bone, among others.

Bone marrow aspiration and blood are cultured in a selective medium (eg, 10% aqueous oxgall) or a nutritious medium (eg, tryptic soy broth) and are incubated at 37°C for at least 7 days. Subcultures are made daily to one selective medium (eg, MacConkey agar) and one inhibitory medium (eg, Salmonella-Shigella agar). Identification of the organism with these conventional culture techniques usually takes 48-72 hours from acquisition.

Table 2. Sensitivities of Cultures[2, 37, 38, 39] (Open Table in a new window)

  Incubation Week 1 Week 2 Week 3 Week 4
Bone marrow aspirate (0.5-1 mL)   90% (may decrease after 5 d of antibiotics)
Blood (10-30 mL), stool, or duodenal aspirate culture 40%-80% ~20% Variable (20%-60%)
Urine   25%-30%, timing unpredictable

Polymerase chain reaction

Polymerase chain reaction (PCR) has been used for the diagnosis of typhoid fever with varying success. Nested PCR, which involves two rounds of PCR using two primers with different sequences within the H1-d flagellin gene of S typhi, offers the best sensitivity and specificity. Combining assays of blood and urine, this technique has achieved a sensitivity of 82.7% and reported specificity of 100%. However, no type of PCR is widely available for the clinical diagnosis of typhoid fever.[40, 41]

Specific serologic tests

Assays that identify Salmonella antibodies or antigens support the diagnosis of typhoid fever, but these results should be confirmed with cultures or DNA evidence.

The Widal test was the mainstay of typhoid fever diagnosis for decades. It is used to measure agglutinating antibodies against H and O antigens of S typhi. Neither sensitive nor specific, the Widal test is no longer an acceptable clinical method.

Indirect hemagglutination, indirect fluorescent Vi antibody, and indirect enzyme-linked immunosorbent assay (ELISA) for immunoglobulin M (IgM) and IgG antibodies to S typhi polysaccharide, as well as monoclonal antibodies against S typhi flagellin,[42] are promising, but the success rates of these assays vary greatly in the literature.

Other nonspecific laboratory studies

Most patients with typhoid fever are moderately anemic, have an elevated erythrocyte sedimentation rate (ESR), thrombocytopenia, and relative lymphopenia.

Most also have a slightly elevated prothrombin time (PT) and activated partial thromboplastin time (aPTT) and decreased fibrinogen levels.

Circulating fibrin degradation products commonly rise to levels seen in subclinical disseminated intravascular coagulation (DIC).

Liver transaminase and serum bilirubin values usually rise to twice the reference range.

Mild hyponatremia and hypokalemia are common.

A serum alanine amino transferase (ALT)–to–lactate dehydrogenase (LDH) ratio of more than 9:1 appears to be helpful in distinguishing typhoid from viral hepatitis. A ratio of greater than 9:1 supports a diagnosis of acute viral hepatitis, while ratio of less than 9:1 supports typhoid hepatitis.[43]


Imaging Studies

Radiography: Radiography of the kidneys, ureters, and bladder (KUB) is useful if bowel perforation (symptomatic or asymptomatic) is suspected.

CT scanning and MRI: These studies may be warranted to investigate for abscesses in the liver or bones, among other sites.



Bone marrow aspiration: The most sensitive method of isolating S typhi is BMA culture (see Lab Studies).


Histologic Findings

The hallmark histologic finding in typhoid fever is infiltration of tissues by macrophages (typhoid cells) that contain bacteria, erythrocytes, and degenerated lymphocytes. Aggregates of these macrophages are called typhoid nodules, which are found most commonly in the intestine, mesenteric lymph nodes, spleen, liver, and bone marrow but may be found in the kidneys, testes, and parotid glands. In the intestines, 4 classic pathologic stages occur in the course of infection: (1) hyperplastic changes, (2) necrosis of the intestinal mucosa, (3) sloughing of the mucosa, and (4) the development of ulcers. The ulcers may perforate into the peritoneal cavity.

In the mesenteric lymph nodes, the sinusoids are enlarged and distended by large collections of macrophages and reticuloendothelial cells. The spleen is enlarged, red, soft, and congested; its serosal surface may have a fibrinous exudate. Microscopically, the red pulp is congested and contains typhoid nodules. The gallbladder is hyperemic and may show evidence of cholecystitis. Liver biopsy specimens from patients with typhoid fever often show cloudy swelling, balloon degeneration with vacuolation of hepatocytes, moderate fatty change, and focal typhoid nodules. Intact typhoid bacilli can be observed at these sites.[2, 4]



The proper treatment approach to typhoid fever depends on whether the illness is complicated or uncomplicated. Complicated typhoid fever is characterized by melena (3% of all hospitalized patients with typhoid fever), serious abdominal discomfort, intestinal perforation, marked neuropsychiatric symptoms, or other severe manifestations. Depending on the adequacy of diagnosis and treatment, complicated disease may develop in up to 10% of treated patients. Delirium, obtundation, stupor, coma, or shock demands a particularly aggressive approach (see Treatment).[34]

Contributor Information and Disclosures

John L Brusch, MD, FACP Assistant Professor of Medicine, Harvard Medical School; Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health Alliance

John L Brusch, MD, FACP is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.


Roberto Corales, DO, AAHIVS Senior Director, HIV Medicine and Clinical Research, Trillium Health

Roberto Corales, DO, AAHIVS is a member of the following medical societies: American Medical Association, International AIDS Society, American Osteopathic Association

Disclosure: Nothing to disclose.

Steven K Schmitt, MD Staff Physician, Department of Infectious Disease, Cleveland Clinic

Steven K Schmitt, MD is a member of the following medical societies: Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Thomas Garvey, MD, JD Primary Care Physician, Burlington Medical Associates; Co-chair, Medical Advisory Committee for the Elimination of Tuberculosis

Thomas Garvey, MD, JD is a member of the following medical societies: American College of Legal Medicine, American College of Physicians, American Society of Law, Medicine & Ethics

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Richard B Brown, MD, FACP Chief, Division of Infectious Diseases, Baystate Medical Center; Professor, Department of Internal Medicine, Tufts University School of Medicine

Richard B Brown, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, Massachusetts Medical Society

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, Oklahoma State Medical Association, Southern Society for Clinical Investigation, Association of Professors of Medicine, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

  1. Papagrigorakis MJ, Synodinos PN, Yapijakis C. Ancient typhoid epidemic reveals possible ancestral strain of Salmonella enterica serovar Typhi. Infect Genet Evol. 2007 Jan. 7(1):126-7. [Medline]. [Full Text].

  2. Christie AB. Infectious Diseases: Epidemiology and Clinical Practice. 4th ed. Edinburgh, Scotland: Churchill Livingstone; 1987.

  3. Raffatellu M, Chessa D, Wilson RP, Tükel C, Akçelik M, Bäumler AJ. Capsule-mediated immune evasion: a new hypothesis explaining aspects of typhoid fever pathogenesis. Infect Immun. 2006 Jan. 74(1):19-27. [Medline].

  4. Parry CM, Hien TT, Dougan G, et al. Typhoid fever. N Engl J Med. 2002 Nov 28. 347(22):1770-82. [Medline]. [Full Text].

  5. de Jong HK, Parry CM, van der Poll T, Wiersinga WJ. Host-pathogen interaction in invasive Salmonellosis. PLoS Pathog. 2012. 8(10):e1002933. [Medline]. [Full Text].

  6. Ramsden AE, Mota LJ, Münter S, Shorte SL, Holden DW. The SPI-2 type III secretion system restricts motility of Salmonella-containing vacuoles. Cell Microbiol. 2007 Oct. 9(10):2517-29. [Medline].

  7. Gonzalez-Escobedo G, Gunn JS. Gallbladder epithelium as a niche for chronic Salmonella carriage. Infect Immun. 2013 Aug. 81(8):2920-30. [Medline]. [Full Text].

  8. Chiou CS, Wei HL, Mu JJ, Liao YS, Liang SY, Liao CH, et al. Salmonella enterica serovar Typhi variants in long-term carriers. J Clin Microbiol. 2013 Feb. 51(2):669-72. [Medline]. [Full Text].

  9. Levine MM, Tacket CO, Sztein MB. Host-Salmonella interaction: human trials. Microbes Infect. 2001 Nov-Dec. 3(14-15):1271-9. [Medline].

  10. Earampamoorthy S, Koff RS. Health hazards of bivalve-mollusk ingestion. Ann Intern Med. 1975 Jul. 83(1):107-10. [Medline]. [Full Text].

  11. Ali S, Vollaard AM, Widjaja S, Surjadi C, van de Vosse E, van Dissel JT. PARK2/PACRG polymorphisms and susceptibility to typhoid and paratyphoid fever. Clin Exp Immunol. 2006 Jun. 144(3):425-31. [Medline].

  12. Ram PK, Naheed A, Brooks WA, Hossain MA, Mintz ED, Breiman RF. Risk factors for typhoid fever in a slum in Dhaka, Bangladesh. Epidemiol Infect. 2007 Apr. 135(3):458-65. [Medline].

  13. Karkey A, Thompson CN, Tran Vu Thieu N, Dongol S, Le Thi Phuong T, Voong Vinh P, et al. Differential epidemiology of Salmonella Typhi and Paratyphi A in Kathmandu, Nepal: a matched case control investigation in a highly endemic enteric fever setting. PLoS Negl Trop Dis. 2013. 7(8):e2391. [Medline]. [Full Text].

  14. Vollaard AM, Ali S, van Asten HA, Widjaja S, Visser LG, Surjadi C, et al. Risk factors for typhoid and paratyphoid fever in Jakarta, Indonesia. JAMA. 2004 Jun 2. 291(21):2607-15. [Medline].

  15. Gotuzzo E, Frisancho O, Sanchez J, Liendo G, Carrillo C, Black RE, et al. Association between the acquired immunodeficiency syndrome and infection with Salmonella typhi or Salmonella paratyphi in an endemic typhoid area. Arch Intern Med. 1991 Feb. 151(2):381-2. [Medline].

  16. Manfredi R, Chiodo F. Salmonella typhi disease in HIV-infected patients: case reports and literature review. Infez Med. 1999. 7(1):49-53. [Medline].

  17. Gordon MA, Graham SM, Walsh AL, Wilson L, Phiri A, Molyneux E, et al. Epidemics of invasive Salmonella enterica serovar enteritidis and S. enterica Serovar typhimurium infection associated with multidrug resistance among adults and children in Malawi. Clin Infect Dis. 2008 Apr 1. 46(7):963-9. [Medline].

  18. Monack DM, Mueller A, Falkow S. Persistent bacterial infections: the interface of the pathogen and the host immune system. Nat Rev Microbiol. 2004 Sep. 2(9):747-65. [Medline].

  19. van de Vosse E, Ali S, de Visser AW, Surjadi C, Widjaja S, Vollaard AM, et al. Susceptibility to typhoid fever is associated with a polymorphism in the cystic fibrosis transmembrane conductance regulator (CFTR). Hum Genet. 2005 Oct. 118(1):138-40. [Medline].

  20. Poolman EM, Galvani AP. Evaluating candidate agents of selective pressure for cystic fibrosis. J R Soc Interface. 2007 Feb 22. 4(12):91-8. [Medline].

  21. Dutta TK, Beeresha, Ghotekar LH. Atypical manifestations of typhoid fever. J Postgrad Med. 2001 Oct-Dec. 47(4):248-51. [Medline].

  22. Lynch MF, Blanton EM, Bulens S, Polyak C, Vojdani J, Stevenson J. Typhoid fever in the United States, 1999-2006. JAMA. 2009 Aug 26. 302(8):859-65. [Medline].

  23. Chau TT, Campbell JI, Galindo CM, Van Minh Hoang N, Diep TS, Nga TT, et al. Antimicrobial drug resistance of Salmonella enterica serovar typhi in asia and molecular mechanism of reduced susceptibility to the fluoroquinolones. Antimicrob Agents Chemother. 2007 Dec. 51(12):4315-23. [Medline].

  24. Crump JA, Luby SP, Mintz ED. The global burden of typhoid fever. Bull World Health Organ. 2004 May. 82(5):346-53. [Medline].

  25. Crump JA, Ram PK, Gupta SK, Miller MA, Mintz ED. Part I. Analysis of data gaps pertaining to Salmonella enterica serotype Typhi infections in low and medium human development index countries, 1984-2005. Epidemiol Infect. 2008 Apr. 136(4):436-48. [Medline].

  26. Mulligan TO. Typhoid fever in young children. Br Med J. 1971 Dec 11. 4(5788):665-7. [Medline].

  27. Rahaman MM, Jamiul AK. Rose spots in shigellosis caused by Shigella dysenteriae type 1 infection. Br Med J. 1977 Oct 29. 2(6095):1123-4. [Medline].

  28. Cunha BA. Malaria or typhoid fever: a diagnostic dilemma?. Am J Med. 2005 Dec. 118(12):1442-3; author reply 1443-4. [Medline].

  29. Woodward TE, Smadel JE. Management of typhoid fever and its complications. Ann Intern Med. 1964 Jan. 60:144-57. [Medline].

  30. Hermans P, Gerard M, van Laethem Y, et al. Pancreatic disturbances and typhoid fever. Scand J Infect Dis. 1991. 23(2):201-5. [Medline].

  31. Butler T, Islam A, Kabir I, et al. Patterns of morbidity and mortality in typhoid fever dependent on age and gender: review of 552 hospitalized patients with diarrhea. Rev Infect Dis. 1991 Jan-Feb. 13(1):85-90. [Medline].

  32. Butler T, Knight J, Nath SK, et al. Typhoid fever complicated by intestinal perforation: a persisting fatal disease requiring surgical management. Rev Infect Dis. 1985 Mar-Apr. 7(2):244-56. [Medline].

  33. Crum NF. Current trends in typhoid Fever. Curr Gastroenterol Rep. 2003 Aug. 5(4):279-86. [Medline].

  34. Huang DB, DuPont HL. Problem pathogens: extra-intestinal complications of Salmonella enterica serotype Typhi infection. Lancet Infect Dis. 2005 Jun. 5(6):341-8. [Medline].

  35. Abdel Wahab MF, el-Gindy IM, Sultan Y, el-Naby HM. Comparative study on different recent diagnostic and therapeutic regimens in acute typhoid fever. J Egypt Public Health Assoc. 1999. 74(1-2):193-205. [Medline].

  36. Wain J, Pham VB, Ha V, Nguyen NM, To SD, Walsh AL, et al. Quantitation of bacteria in bone marrow from patients with typhoid fever: relationship between counts and clinical features. J Clin Microbiol. 2001 Apr. 39(4):1571-6. [Medline].

  37. Escamilla J, Florez-Ugarte H, Kilpatrick ME. Evaluation of blood clot cultures for isolation of Salmonella typhi, Salmonella paratyphi-A, and Brucella melitensis. J Clin Microbiol. 1986 Sep. 24(3):388-90. [Medline].

  38. Gilman RH, Terminel M, Levine MM, Hernandez-Mendoza P, Hornick RB. Relative efficacy of blood, urine, rectal swab, bone-marrow, and rose-spot cultures for recovery of Salmonella typhi in typhoid fever. Lancet. 1975 May 31. 1(7918):1211-3. [Medline].

  39. Farooqui BJ, Khurshid M, Ashfaq MK, Khan MA. Comparative yield of Salmonella typhi from blood and bone marrow cultures in patients with fever of unknown origin. J Clin Pathol. 1991 Mar. 44(3):258-9. [Medline].

  40. Ambati SR, Nath G, Das BK. Diagnosis of typhoid fever by polymerase chain reaction. Indian J Pediatr. 2007 Oct. 74(10):909-13. [Medline].

  41. Song JH, Cho H, Park MY, et al. Detection of Salmonella typhi in the blood of patients with typhoid fever by polymerase chain reaction. J Clin Microbiol. 1993 Jun. 31(6):1439-43. [Medline].

  42. Sadallah F, Brighouse G, Del Giudice G, et al. Production of specific monoclonal antibodies to Salmonella typhi flagellin and possible application to immunodiagnosis of typhoid fever. J Infect Dis. 1990 Jan. 161(1):59-64. [Medline].

  43. Balasubramanian S, Kaarthigeyan K, Srinivas S, Rajeswari R. Serum ALT: LDH Ratio in Typhoid Fever and Acute Viral Hepatitis. Indian Pediatr. 2009 Jul 1. [Medline].

  44. Capoor MR, Nair D, Deb M, Aggarwal P. Enteric fever perspective in India: emergence of high-level ciprofloxacin resistance and rising MIC to cephalosporins. J Med Microbiol. 2007 Aug. 56:1131-2. [Medline].

  45. Pai H, Byeon JH, Yu S, Lee BK, Kim S. Salmonella enterica serovar typhi strains isolated in Korea containing a multidrug resistance class 1 integron. Antimicrob Agents Chemother. 2003 Jun. 47(6):2006-8. [Medline].

  46. Mamun KZ, Tabassum S, Ashna SM, Hart CA. Molecular analysis of multi-drug resistant Salmonella typhi from urban paediatric population of Bangladesh. Bangladesh Med Res Counc Bull. 2004 Dec. 30(3):81-6. [Medline].

  47. Ahmed D, D'Costa LT, Alam K, Nair GB, Hossain MA. Multidrug-resistant Salmonella enterica serovar typhi isolates with high-level resistance to ciprofloxacin in Dhaka, Bangladesh. Antimicrob Agents Chemother. 2006 Oct. 50(10):3516-7. [Medline].

  48. Zhanel GG, Smith HJ. Flouroquinolone resistance-associated gene mutations in Streptococcus pneumoniae. Fuchs J, Podda M, eds. Encyclopedia of Medical Genomics and Proteomics. CRC Press; 2004. 497-8. [Full Text].

  49. Turner AK, Nair S, Wain J. The acquisition of full fluoroquinolone resistance in Salmonella Typhi by accumulation of point mutations in the topoisomerase targets. J Antimicrob Chemother. 2006 Oct. 58(4):733-40. [Medline].

  50. Effa EE, Lassi ZS, Critchley JA, et al. Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever). Cochrane Database Syst Rev. 2011 Oct 5. CD004530. [Medline].

  51. Arjyal A, Pandit A. Treatment of enteric fever. J Infect Dev Ctries. 2008 Dec 1. 2(6):426-30. [Medline].

  52. Kundu R, Ganguly N, Ghosh TK, et al. IAP Task Force Report: management of enteric fever in children. Indian Pediatr. 2006 Oct. 43(10):884-7. [Medline].

  53. Islam MN, Rahman ME, Rouf MA, Islam MN, Khaleque MA, Siddika M, et al. Efficacy of azithromycin in the treatment of childhood typhoid Fever. Mymensingh Med J. 2007 Jul. 16(2):149-53. [Medline].

  54. Acosta C et al. Background document: The diagnosis, treatment and prevention of typhoid fever. 07/2003. Available at

  55. National Antimicrobial Resistance Monitoring System 2012 Human Isolates Final Report. Available at

  56. Dutta S, Sur D, Manna B, Bhattacharya SK, Deen JL, Clemens JD. Rollback of Salmonella enterica serotype Typhi resistance to chloramphenicol and other antimicrobials in Kolkata, India. Antimicrob Agents Chemother. 2005 Apr. 49(4):1662-3. [Medline].

  57. Vaccines and Biologicals. World Health Organization. May, 2003.

  58. Cooke FJ, Wain J. The emergence of antibiotic resistance in typhoid fever. Travel Med Infect Dis. 2004 May. 2(2):67-74. [Medline].

  59. Trivedi NA, Shah PC. A meta-analysis comparing the safety and efficacy of azithromycin over the alternate drugs used for treatment of uncomplicated enteric fever. J Postgrad Med. 2012 Apr. 58(2):112-8. [Medline].

  60. Hoffman SL, Punjabi NH, Kumala S, et al. Reduction of mortality in chloramphenicol-treated severe typhoid fever by high-dose dexamethasone. N Engl J Med. 1984 Jan 12. 310(2):82-8. [Medline].

  61. Bhutta ZA. Current concepts in the diagnosis and treatment of typhoid fever. BMJ. 2006 Jul 8. 333(7558):78-82. [Medline].

  62. Rogerson SJ, Spooner VJ, Smith TA, et al. Hydrocortisone in chloramphenicol-treated severe typhoid fever in Papua New Guinea. Trans R Soc Trop Med Hyg. 1991 Jan-Feb. 85(1):113-6. [Medline].

  63. Jackson BR, Iqbal S, Mahon B. Updated recommendations for the use of typhoid vaccine - advisory committee on immunization practices, United States, 2015. MMWR Morb Mortal Wkly Rep. 2015 Mar 27. 64(11):305-8. [Medline].

  64. Schwartz E, Shlim DR, Eaton M, Jenks N, Houston R. The effect of oral and parenteral typhoid vaccination on the rate of infection with Salmonella typhi and Salmonella paratyphi A among foreigners in Nepal. Arch Intern Med. 1990 Feb. 150(2):349-51. [Medline].

  65. Pakkanen SH, Kantele JM, Kantele A. Cross-reactive immune response induced by the vi capsular polysaccharide typhoid vaccine against salmonella paratyphi strains. Scand J Immunol. 2014 Mar. 79(3):222-9. [Medline].

  66. Acharya IL, Lowe CU, Thapa R, et al. Prevention of typhoid fever in Nepal with the Vi capsular polysaccharide of Salmonella typhi. A preliminary report. N Engl J Med. 1987 Oct 29. 317(18):1101-4. [Medline].

  67. Sur D, Ochiai RL, Bhattacharya SK, Ganguly NK, Ali M, Manna B, et al. A cluster-randomized effectiveness trial of Vi typhoid vaccine in India. N Engl J Med. 2009 Jul 23. 361(4):335-44. [Medline].

  68. Hanel RA, Araujo JC, Antoniuk A, et al. Multiple brain abscesses caused by Salmonella typhi: case report. Surg Neurol. 2000 Jan. 53(1):86-90. [Medline].

  69. Koul PA, Wani JI, Wahid A, et al. Pulmonary manifestations of multidrug-resistant typhoid fever. Chest. 1993 Jul. 104(1):324-5. [Medline].

  70. Khan M, Coovadia Y, Sturm AW. Typhoid fever complicated by acute renal failure and hepatitis: case reports and review. Am J Gastroenterol. 1998 Jun. 93(6):1001-3. [Medline].

  71. Sitprija V, Pipantanagul V, Boonpucknavig V, et al. Glomerulitis in typhoid fever. Ann Intern Med. 1974 Aug. 81(2):210-3. [Medline].

  72. Baker NM, Mills AE, Rachman I, et al. Haemolytic-uraemic syndrome in typhoid fever. Br Med J. 1974 Apr 13. 2(5910):84-7. [Medline].

  73. Naidoo PM, Yan CC. Typhoid polymyositis. S Afr Med J. 1975 Nov 8. 49(47):1975-6. [Medline].

  74. Breakey WR, Kala AK. Typhoid catatonia responsive to ECT. Br Med J. 1977 Aug 6. 2(6083):357-9. [Medline].

  75. Ackers ML, Puhr ND, Tauxe RV, et al. Laboratory-based surveillance of Salmonella serotype Typhi infections in the United States: antimicrobial resistance on the rise. JAMA. 2000 May 24-31. 283(20):2668-73. [Medline]. [Full Text].

  76. Adam D. Use of quinolones in pediatric patients. Rev Infect Dis. 1989 Jul-Aug. 11 Suppl 5:S1113-6. [Medline].

  77. Akalin HE. Quinolones in the treatment of typhoid fever. Drugs. 1999. 58 Suppl 2:52-4. [Medline].

  78. Ambrosch F, Fritzell B, Gregor J, et al. Combined vaccination against yellow fever and typhoid fever: a comparative trial. Vaccine. 1994 May. 12(7):625-8. [Medline].

  79. Anand AC, Kataria VK, Singh W, et al. Epidemic multiresistant enteric fever in eastern India. Lancet. 1990 Feb 10. 335(8685):352. [Medline].

  80. Angorn IB, Pillay SP, Hegarty M, et al. Typhoid perforation of the ileum: A therapeutic dilemma. S Afr Med J. 1975 May 3. 49(19):781-4. [Medline].

  81. Cunha BA. Antibiotic Essentials. 7th Ed. Royal Oak, MI: Physicians Press; 2008.

  82. Archampong EQ. Operative treatment of typhoid perforation of the bowel. Br Med J. 1969 Aug 2. 3(5665):273-6. [Medline].

  83. Ashcroft MT, Singh B, Nicholson CC, et al. A seven-year field trial of two typhoid vaccines in Guyana. Lancet. 1967 Nov 18. 2(7525):1056-9. [Medline].

  84. Bitar R, Tarpley J. Intestinal perforation in typhoid fever: a historical and state-of-the-art review. Rev Infect Dis. 1985 Mar-Apr. 7(2):257-71. [Medline].

  85. Blaser MJ, Hickman FW, Farmer JJ 3rd, et al. Salmonella typhi: the laboratory as a reservoir of infection. J Infect Dis. 1980 Dec. 142(6):934-8. [Medline].

  86. Blaser MJ, Newman LS. A review of human salmonellosis: I. Infective dose. Rev Infect Dis. 1982 Nov-Dec. 4(6):1096-106. [Medline].

  87. Bodhidatta L, Taylor DN, Thisyakorn U, et al. Control of typhoid fever in Bangkok, Thailand, by annual immunization of schoolchildren with parenteral typhoid vaccine. Rev Infect Dis. 1987 Jul-Aug. 9(4):841-5. [Medline].

  88. Brumell JH, Grinstein S. Salmonella redirects phagosomal maturation. Curr Opin Microbiol. 2004 Feb. 7(1):78-84. [Medline]. [Full Text].

  89. Butler T, Rumans L, Arnold K. Response of typhoid fever caused by chloramphenicol-susceptible and chloramphenicol-resistant strains of Salmonella typhi to treatment with trimethoprim-sulfamethoxazole. Rev Infect Dis. 1982 Mar-Apr. 4(2):551-61. [Medline].

  90. Calva JJ, Ruiz-Palacios GM. Salmonella hepatitis: detection of salmonella antigens in the liver of patients with typhoid fever. J Infect Dis. 1986 Aug. 154(2):373-4. [Medline].

  91. Cancellieri V, Fara GM. Demonstration of specific IgA in human feces after immunization with live Ty21a Salmonella typhi vaccine. J Infect Dis. 1985 Mar. 151(3):482-4. [Medline].

  92. Capoor MR, Rawat D, Nair D, Hasan AS, Deb M, Aggarwal P, et al. In vitro activity of azithromycin, newer quinolones and cephalosporins in ciprofloxacin-resistant Salmonella causing enteric fever. J Med Microbiol. 2007 Nov. 56:1490-4. [Medline].

  93. Carcelen A, Chirinos J, Yi A. Furazolidone and chloramphenicol for treatment of typhoid fever. Scand J Gastroenterol Suppl. 1989. 169:19-23. [Medline].

  94. Centers for Disease Control and Prevention. CDC Typhoid Immunization Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 1994. 43(RR-14):1-7.

  95. Coovadia YM, Gathiram V, Bhamjee A, et al. An outbreak of multiresistant Salmonella typhi in South Africa. Q J Med. 1992 Feb. 82(298):91-100. [Medline].

  96. Crosa JH, Brenner DJ, Ewing WH, et al. Molecular relationships among the Salmonelleae. J Bacteriol. 1973 Jul. 115(1):307-15. [Medline].

  97. Cryz SJ Jr. Post-marketing experience with live oral Ty21a vaccine. Lancet. 1993 Jan 2. 341(8836):49-50. [Medline].

  98. Cumberland NS, St Clair Roberts J, Arnold WS, et al. Typhoid Vi: a less reactogenic vaccine. J Int Med Res. 1992 Jun. 20(3):247-53. [Medline].

  99. Cunha BA. Osler on typhoid fever: differentiating typhoid from typhus and malaria. Infect Dis Clin North Am. 2004 Mar. 18(1):111-25. [Medline].

  100. Cunha BA. Typhoid fever: the temporal relations of key clinical diagnostic points. Lancet Infect Dis. 2006 Jun. 6(6):318-20; author reply 320-1. [Medline].

  101. Dashti AA, Jadaon MM, Habeeb F, West PW, Panigrahi D, Amyes SG. Salmonella enterica Serotype typhi in Kuwait and its reduced susceptibility to ciprofloxacin. J Chemother. 2008 Jun. 20(3):297-302. [Medline].

  102. Djemgou PC, Gatsing D, Hegazy ME, El-Hamd Mohamed AH, Ngandeu F, Tane P, et al. Turrealabdane, turreanone and an antisalmonellal agent from Turraeanthus africanus. Planta Med. 2010 Feb. 76(2):165-71. [Medline].

  103. Dong B, Galindo CM, Shin E, Acosta CJ, Page AL, Wang M, et al. Optimizing typhoid fever case definitions by combining serological tests in a large population study in Hechi City, China. Epidemiol Infect. 2007 Aug. 135(6):1014-20. [Medline].

  104. Duggan MB, Beyer L. Enteric fever in young Yoruba children. Arch Dis Child. 1975 Jan. 50(1):67-71. [Medline].

  105. Dunne EF, Fey PD, Kludt P, et al. Emergence of domestically acquired ceftriaxone-resistant Salmonella infections associated with AmpC beta-lactamase. JAMA. 2000 Dec 27. 284(24):3151-6. [Medline].

  106. Edelman R, Levine MM. Summary of an international workshop on typhoid fever. Rev Infect Dis. 1986 May-Jun. 8(3):329-49. [Medline].

  107. Effa EE, Bukirwa H. Azithromycin for treating uncomplicated typhoid and paratyphoid fever (enteric fever). Cochrane Database Syst Rev. 2008 Oct 8. CD006083. [Medline].

  108. Farid Z, Higashi GI, Bassily S, et al. Letter: Immune-complex disease in typhoid and paratyphoid fevers. Ann Intern Med. 1975 Sep. 83(3):432. [Medline].

  109. Farmer JJ. Enterobacteriaceae: introduction and identification. Murray PR, Baron EF, Pfaller MA, eds. Manual of Clinical Microbiology. 6th ed. Washington, DC: American Society for Microbiology; 1995. 438-49.

  110. Ferreccio C, Levine MM, Manterola A, Rodriguez G, Rivara I, Prenzel I, et al. Benign bacteremia caused by Salmonella typhi and paratyphi in children younger than 2 years. J Pediatr. 1984 Jun. 104(6):899-901. [Medline].

  111. Ferreccio C, Levine MM, Rodriguez H, et al. Comparative efficacy of two, three, or four doses of TY21a live oral typhoid vaccine in enteric-coated capsules: a field trial in an endemic area. J Infect Dis. 1989 Apr. 159(4):766-9. [Medline].

  112. Ferreccio C, Morris JG, Valdivieso C, et al. Efficacy of ciprofloxacin in the treatment of chronic typhoid carriers. J Infect Dis. 1988 Jun. 157(6):1235-9. [Medline].

  113. Frenck RW Jr, Nakhla I, Sultan Y, Bassily SB, Girgis YF, David J, et al. Azithromycin versus ceftriaxone for the treatment of uncomplicated typhoid fever in children. Clin Infect Dis. 2000 Nov. 31(5):1134-8. [Medline].

  114. Frenck RW, Nakhla I, Sultan Y, et al. Azithromycin versus ceftriaxone for the treatment of uncomplicated typhoid fever in children. Clin Infect Dis. 2000. 31:134-1138. [Medline].

  115. Ghosh SK. Typhoid fever in present-day Britain. Public Health. 1974 Jan. 88(2):71-8. [Medline].

  116. Gilman RH, Hornick RB, Woodard WE, et al. Evaluation of a UDP-glucose-4-epimeraseless mutant of Salmonella typhi as a liver oral vaccine. J Infect Dis. 1977 Dec. 136(6):717-23. [Medline].

  117. Gilman RH, Terminel M, Levine MM, et al. Relative efficacy of blood, urine, rectal swab, bone-marrow, and rose- spot cultures for recovery of Salmonella typhi in typhoid fever. Lancet. 1975 May 31. 1(7918):1211-3. [Medline].

  118. Gorden J, Small PL. Acid resistance in enteric bacteria. Infect Immun. 1993 Jan. 61(1):364-7. [Medline].

  119. Gordon MA. Salmonella infections in immunocompromised adults. J Infect. 2008 Jun. 56(6):413-22. [Medline].

  120. Gotuzzo E, Frisancho O, Sanchez J, Liendo G, Carrillo C, Black RE, et al. Association between the acquired immunodeficiency syndrome and infection with Salmonella typhi or Salmonella paratyphi in an endemic typhoid area. Arch Intern Med. 1991 Feb. 151(2):381-2. [Medline].

  121. Gotuzzo E, Guerra JG, Benavente L, et al. Use of norfloxacin to treat chronic typhoid carriers. J Infect Dis. 1988 Jun. 157(6):1221-5. [Medline].

  122. Gray LD. Escherichia, Salmonella, Shigella, and Yersinia. Murray PR, Baron EJ, Pfaller MA, eds. Manual of Clinical Microbiology. 6th ed. Washington, DC: American Society for Microbiology; 1995. 450-6.

  123. Greisman SE, Woodward TE, Hornick RB, Snyder MJ, Carozza FA Jr. Typhoid fever: a study of pathogenesis and physiologic abnormalities. Trans Am Clin Climatol Assoc. 1961. 73:146-61. [Medline].

  124. Gulati S, Marwaha RK, Prakash D, et al. Multi-drug-resistant Salmonella typhi--a need for therapeutic reappraisal. Ann Trop Paediatr. 1992. 12(2):137-41. [Medline].

  125. Gupta A. Multidrug-resistant typhoid fever in children: epidemiology and therapeutic approach. Pediatr Infect Dis J. 1994 Feb. 13(2):134-40. [Medline].

  126. Gupta SP, Gupta MS, Bhardwaj S, et al. Current clinical patterns of typhoid fever: a prospective study. J Trop Med Hyg. 1985 Dec. 88(6):377-81. [Medline].

  127. Hensel M. Salmonella pathogenicity island 2. Mol Microbiol. 2000 Jun. 36(5):1015-23. [Medline].

  128. Herzog C. Chemotherapy of typhoid fever: a review of literature. Infection. 1976. 4(3):166-73. [Medline].

  129. Herzog C. New trends in the chemotherapy of typhoid fever. Acta Trop. 1980 Sep. 37(3):275-80. [Medline].

  130. Hoffman SL, Edman DC, Punjabi NH, et al. Bone marrow aspirate culture superior to streptokinase clot culture and 8 ml 1:10 blood-to-broth ratio blood culture for diagnosis of typhoid fever. Am J Trop Med Hyg. 1986 Jul. 35(4):836-9. [Medline].

  131. Hoffman SL, Flanigan TP, Klaucke D, et al. The Widal slide agglutination test, a valuable rapid diagnostic test in typhoid fever patients at the Infectious Diseases Hospital of Jakarta. Am J Epidemiol. 1986 May. 123(5):869-75. [Medline].

  132. Hoffman SL, Punjabi NH, Rockhill RC, et al. Duodenal string-capsule culture compared with bone-marrow, blood, and rectal-swab cultures for diagnosing typhoid and paratyphoid fever. J Infect Dis. 1984 Feb. 149(2):157-61. [Medline].

  133. Hornick RB, DuPont HL, Levine MM, et al. Efficacy of a live oral typhoid vaccine in human volunteers. Dev Biol Stand. 1976. 33:89-92. [Medline].

  134. Hornick RB, Greisman SE, Woodward TE, et al. Typhoid fever: pathogenesis and immunologic control. N Engl J Med. 1970 Sep 24. 283(13):686-91. [Medline].

  135. Hornick RB, Greisman SE, Woodward TE, et al. Typhoid fever: pathogenesis and immunologic control. 2. N Engl J Med. 1970 Oct 1. 283(14):739-46. [Medline].

  136. Hornick RB, Griesman S. On the pathogenesis of typhoid fever. Arch Intern Med. 1978 Mar. 138(3):357-9. [Medline].

  137. Hornick RB, Woodward TE. Appraisal of typhoid vaccine in experimentally infected human subjects. Trans Am Clin Climatol Assoc. 1967. 78:70-8. [Medline].

  138. Huckstep RL. Recent advances in the surgery of typhoid fever. Ann R Coll Surg Engl. 1960 Apr. 26:207-30. [Medline].

  139. Huckstep RL. Typhoid Fever and Other Salmonella Infections. Edinburgh, Scotland: Churchill Livingstone; 1962.

  140. Joshi N, Rajeshwari K, Dubey AP, Singh T, Kaur R. Clinical spectrum of fever of unknown origin among Indian children. Ann Trop Paediatr. 2008 Dec. 28(4):261-6. [Medline].

  141. Keitel WA, Bond NL, Zahradnik JM, et al. Clinical and serological responses following primary and booster immunization with Salmonella typhi Vi capsular polysaccharide vaccines. Vaccine. 1994. 12(3):195-9. [Medline].

  142. Keusch GT. Antimicrobial therapy for enteric infections and typhoid fever: state of the art. Rev Infect Dis. 1988 Jan-Feb. 10 Suppl 1:S199-205. [Medline].

  143. Khosla SN. Changing patterns of typhoid (a reappraisal). Asian Med J. 1982. 25:185-98.

  144. Khosla SN. Typhoid hepatitis. Postgrad Med J. 1990 Nov. 66(781):923-5. [Medline].

  145. Kim JP, Oh SK, Jarrett F. Management of ileal perforation due to typhoid fever. Ann Surg. 1975 Jan. 181(1):88-91. [Medline].

  146. Klotz SA, Jorgensen JH, Buckwold FJ, et al. Typhoid fever. An epidemic with remarkably few clinical signs and symptoms. Arch Intern Med. 1984 Mar. 144(3):533-7. [Medline].

  147. Klugman KP, Gilbertson IT, Koornhof HJ, et al. Protective activity of Vi capsular polysaccharide vaccine against typhoid fever. Lancet. 1987 Nov 21. 2(8569):1165-9. [Medline].

  148. Klugman KP, Koornhof HJ, Robbins JB. Immunogenicity and protective efficacy of Vi vaccine against typhoid fever three years after immunization (abstract). Second Asia-Pacific Symposium on Typhoid Fever and Other Salmonellosis. Bangkok, Thailand: 1994.

  149. Kohbata S, Yokoyama H, Yabuuchi E. Cytopathogenic effect of Salmonella typhi GIFU 10007 on M cells of murine ileal Peyer's patches in ligated ileal loops: an ultrastructural study. Microbiol Immunol. 1986. 30(12):1225-37. [Medline].

  150. Lesser, CF, Miller, SI. Salmonellosis. Harrison's Principles of Internal Medicine. 16th ed. 2005. 1: 898-902.

  151. Levine MM, Ferreccio C, Black RE, et al. Large-scale field trial of Ty21a live oral typhoid vaccine in enteric-coated capsule formulation. Lancet. 1987 May 9. 1(8541):1049-52. [Medline].

  152. Levine MM, Taylor DN, Ferreccio C. Typhoid vaccines come of age. Pediatr Infect Dis J. 1989 Jun. 8(6):374-81. [Medline].

  153. Luby, S, Mintz, E. Typhoid Fever. Health Information for International Travel (CDC). 2005-2006. Web link:[Full Text].

  154. Ly KT, Casanova JE. Mechanisms of Salmonella entry into host cells. Cell Microbiol. 2007 Sep. 9(9):2103-11. [Medline].

  155. Mandal BK. Salmonella infections. Manson-Bahr, PEC, Bell DR, Manson P, eds. Manson’s Tropical Medicine. 20th ed. London, UK: Saunders; 1996. 849-63.

  156. Mandal BK. Modern treatment of typhoid fever. J Infect. 1991 Jan. 22(1):1-4. [Medline].

  157. Mani V, Brennand J, Mandal BK. Invasive illness with Salmonella virchow infection. Br Med J. 1974 Apr 20. 2(5911):143-4. [Medline].

  158. Maskalyk J. Typhoid fever. CMAJ. 2003 Jul 22. 169(2):132. [Medline].

  159. Meier DE, Imediegwu OO, Tarpley JL. Perforated typhoid enteritis: operative experience with 108 cases. Am J Surg. 1989 Apr. 157(4):423-7. [Medline].

  160. Murphy JR, Baqar S, Munoz C, et al. Characteristics of humoral and cellular immunity to Salmonella typhi in residents of typhoid-endemic and typhoid-free regions. J Infect Dis. 1987 Dec. 156(6):1005-9. [Medline].

  161. Nardiello S, Pizzella T, Russo M, et al. Serodiagnosis of typhoid fever by enzyme-linked immunosorbent assay determination of anti-Salmonella typhi lipopolysaccharide antibodies. J Clin Microbiol. 1984 Oct. 20(4):718-21. [Medline].

  162. Ochiai RL, Acosta CJ, Danovaro-Holliday MC, Baiqing D, Bhattacharya SK, Agtini MD, et al. A study of typhoid fever in five Asian countries: disease burden and implications for controls. Bull World Health Organ. 2008 Apr. 86(4):260-8. [Medline]. [Full Text].

  163. Osuntokun BO, Bademosi O, Ogunremi K, et al. Neuropsychiatric manifestations of typhoid fever in 959 patients. Arch Neurol. 1972 Jul. 27(1):7-13. [Medline].

  164. Parker MT. Salmonella. Wilson G, Miles A, Parker MT, eds. Topley and Wilson’s Principles of Bacteriology, Virology and Immunity. 7th ed. Baltimore, Md: Williams & Wilkins; 1983. 332-55.

  165. Parry CM, Karunanayake L, Coulter JB, Beeching NJ. Test for quinolone resistance in typhoid fever. BMJ. 2006 Jul 29. 333(7561):260-1. [Medline].

  166. Parry CM, Threlfall EJ. Antimicrobial resistance in typhoidal and nontyphoidal salmonellae. Curr Opin Infect Dis. 2008 Oct. 21(5):531-8. [Medline].

  167. Parry, CM. Epidemiological and Clinical Aspects of Typhoid Fever. Mastroeni, P and Maskell, D. Salmonella InfectionsClinical, Immunological, and Molecular Aspects. 1st. Nw York, New York: 2006. 1-24/1. [Full Text].

  168. Pithie AD, Wood MJ. Treatment of typhoid fever and infectious diarrhoea with ciprofloxacin. J Antimicrob Chemother. 1990 Dec. 26 Suppl F:47-53. [Medline].

  169. Polish Typhoid Committee. Controlled field trials and laboratory studies on the effectiveness of typhoid vaccines in Poland, 1961-64. Bull World Health Organ. 1966. 34(2):211-22. [Medline].

  170. Punjabi NH, Hoffman SL, Edman DC, et al. Treatment of severe typhoid fever in children with high dose dexamethasone. Pediatr Infect Dis J. 1988 Aug. 7(8):598-600. [Medline].

  171. Punjabi NH, Hoffman SL, Edman DC, Sukri N, Laughlin LW, Pulungsih SP, et al. Treatment of severe typhoid fever in children with high dose dexamethasone. Pediatr Infect Dis J. 1988 Aug. 7(8):598-600. [Medline].

  172. Raffatellu M, Chessa D, Wilson RP, Dusold R, Rubino S, Bäumler AJ. The Vi capsular antigen of Salmonella enterica serotype Typhi reduces Toll-like receptor-dependent interleukin-8 expression in the intestinal mucosa. Infect Immun. 2005 Jun. 73(6):3367-74. [Medline].

  173. Ramachandran S, Wickremesinghe HR, Perera MV. Acute disseminated encephalomyelitis in typhoid fever. Br Med J. 1975 Mar 1. 1(5956):494-5. [Medline].

  174. Robbins JD, Robbins JB. Reexamination of the protective role of the capsular polysaccharide (Vi antigen) of Salmonella typhi. J Infect Dis. 1984 Sep. 150(3):436-49. [Medline].

  175. Rowland HA. The complications of typhoid fever. J Trop Med Hyg. 1961 Jun. 64:143-52. [Medline].

  176. Rowland HA. The treatment of typhoid fever. J Trop Med Hyg. 1961 May. 64:101-10. [Medline].

  177. Rubin FA, Kopecko DJ, Sack RB, et al. Evaluation of a DNA probe for identifying Salmonella typhi in Peruvian and Indonesian bacterial isolates. J Infect Dis. 1988 May. 157(5):1051-3. [Medline].

  178. Rubin FA, McWhirter PD, Punjabi NH, et al. Use of a DNA probe to detect Salmonella typhi in the blood of patients with typhoid fever. J Clin Microbiol. 1989 May. 27(5):1112-4. [Medline].

  179. Rubin RH, Weinstein L. Salmonellosis: Microbiologic, Pathologic, and Clinical Features. New York, NY: Stratton Intercontinental; 1977.

  180. Ryan CA, Hargrett-Bean NT, Blake PA. Salmonella typhi infections in the United States, 1975-1984: increasing role of foreign travel. Rev Infect Dis. 1989 Jan-Feb. 11(1):1-8. [Medline].

  181. Salerno-Goncalves R, Pasetti MF, Sztein MB. Characterization of CD8(+) effector T cell responses in volunteers immunized with Salmonella enterica serovar Typhi strain Ty21a typhoid vaccine. J Immunol. 2002 Aug 15. 169(4):2196-203. [Medline].

  182. Salerno-Gonçalves R, Wyant TL, Pasetti MF, Fernandez-Viña M, Tacket CO, Levine MM, et al. Concomitant induction of CD4+ and CD8+ T cell responses in volunteers immunized with Salmonella enterica serovar typhi strain CVD 908-htrA. J Immunol. 2003 Mar 1. 170(5):2734-41. [Medline].

  183. Scottish Home and Health Department. The Aberdeen Typhoid Outbreak. Edinburgh:. HMSO. 1964.

  184. Scragg JN, Rubidge CJ. Amoxycillin in the treatment of typhoid fever in children. Am J Trop Med Hyg. 1975 Sep. 24(5):860-5. [Medline].

  185. Scully BE, Nakatomi M, Ores C, et al. Ciprofloxacin therapy in cystic fibrosis. Am J Med. 1987 Apr 27. 82(4A):196-201. [Medline].

  186. Simanjuntak CH, Paleologo FP, Punjabi NH, et al. Oral immunisation against typhoid fever in Indonesia with Ty21a vaccine. Lancet. 1991 Oct 26. 338(8774):1055-9. [Medline].

  187. Smith T. The hog-cholera group of bacteria. US Bur Anim Ind Bull. 1894. 6:6-40.

  188. Soe GB, Overturf GD. Treatment of typhoid fever and other systemic salmonelloses with cefotaxime, ceftriaxone, cefoperazone, and other newer cephalosporins. Rev Infect Dis. 1987 Jul-Aug. 9(4):719-36. [Medline].

  189. Spanò S, Ugalde JE, Galán JE. Delivery of a Salmonella Typhi exotoxin from a host intracellular compartment. Cell Host Microbe. 2008 Jan 17. 3(1):30-8. [Medline].

  190. Spreng S, Dietrich G, Weidinger G. Rational design of Salmonella-based vaccination strategies. Methods. 2006 Feb. 38(2):133-43. [Medline].

  191. Stanley PJ, Flegg PJ, Mandal BK, et al. Open study of ciprofloxacin in enteric fever. J Antimicrob Chemother. 1989 May. 23(5):789-91. [Medline].

  192. Steinberg EB, Bishop R, Haber P, Dempsey AF, Hoekstra RM, Nelson JM, et al. Typhoid fever in travelers: who should be targeted for prevention?. Clin Infect Dis. 2004 Jul 15. 39(2):186-91. [Medline].

  193. Stoleru GH, Le Minor L, Lheritier AM. Polynucleotide sequence divergence among strains of Salmonella sub-genus IV and closely related organisms. Ann Microbiol (Paris). 1976 May-Jun. 127(4):477-86. [Medline].

  194. Stuart BM, Pullen RL. Typhoid: clinical analysis of three hundred and sixty cases. Arch Intern Med. 1946. 78:629-61.

  195. Thaver D, Zaidi AK, Critchley J, Azmatullah A, Madni SA, Bhutta ZA. A comparison of fluoroquinolones versus other antibiotics for treating enteric fever: meta-analysis. BMJ. 2009 Jun 3. 338:b1865. [Medline]. [Full Text].

  196. Thaver D, Zaidi AK, Critchley JA, Azmatullah A, Madni SA, Bhutta ZA. Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever). Cochrane Database Syst Rev. 2008 Oct 8. CD004530. [Medline].

  197. Thielman, NM, Guerrant, RL. Enteric Fever and Other Causes of Abdominal Symptoms with Fever. Principles and Practice of Infectious Diseases. 6th ed. 2005. 1273-86.

  198. Tran TH, Bethell DB, Nguyen TT, et al. Short course of ofloxacin for treatment of multidrug-resistant typhoid. Clin Infect Dis. 1995 Apr. 20(4):917-23. [Medline].

  199. Uneke CJ. Concurrent malaria and typhoid fever in the tropics: the diagnostic challenges and public health implications. J Vector Borne Dis. 2008 Jun. 45(2):133-42. [Medline].

  200. Vollaard AM, Ali S, van Asten HA, Widjaja S, Visser LG, Surjadi C, et al. Risk factors for typhoid and paratyphoid fever in Jakarta, Indonesia. JAMA. 2004 Jun 2. 291(21):2607-15. [Medline].

  201. Walker DH, Le TP, Hoffman S, et al. Typhoid fever. Tropical Infectious Diseases: Principles, Pathogens, and Practice. New York, NY: Churchill Livingstone; 1999.

  202. Woodward TE, Hall HE, Dias-Rivera R, et al. Treatment of typhoid fever. II. Control of clinical manifestations with cortisone. Ann Intern Med. 1951 Jan. 34(1):10-9. [Medline].

  203. Yanagi D, de Vries GC, Rahardjo D, Alimsardjono L, Wasito EB, De I, et al. Emergence of fluoroquinolone-resistant strains of Salmonella enterica in Surabaya, Indonesia. Diagn Microbiol Infect Dis. 2009 Aug. 64(4):422-6. [Medline].

  204. Yugoslav Typhoid Commission. A controlled field trial of the effectiveness of acetone-dried and inactivated and heat-phenol-inactivated typhoid vaccines in Yugoslavia. Bull WHO. 1964. 30:623-30.

  205. Zinder ND, Lederberg J. Genetic exchange in Salmonella. J Bacteriol. 1952 Nov. 64(5):679-99. [Medline].

Life cycle of Salmonella typhi.
Table 1. Incidence and Timing of Various Manifestations of Untreated Typhoid Fever [2, 31, 32, 33, 34, 35]
  Incubation Week 1 Week 2 Week 3 Week 4 Post
Systemic Recovery phase or death (15% of untreated cases) 10%-20% relapse; 3%-4% chronic carriers;

long-term neurologic sequelae (extremely rare);

gallbladder cancer (RR=167; carriers)

Stepladder fever pattern or insidious onset fever   Very commona Very common
Acute high fever   Very rareb    
Chills   Almost allc
Rigors   Uncommon
Anorexia   Almost all
Diaphoresis   Very common
Malaise   Almost all Almost all Typhoid state (common)
Insomnia     Very common
Confusion/delirium   Commond Very common
Psychosis   Very rare Common  
Catatonia   Very rare    
Frontal headache

(usually mild)

  Very common    
Meningeal signs   Raree Rare  
Parkinsonism   Very rare    
Ear, nose, and throat
Coated tongue   Very common    
Sore throatf        
Mild cough   Common    
Bronchitic cough   Common    
Rales   Common    
Pneumonia   Rare (lobar) Rare Common


Dicrotic pulse   Rare Common
Myocarditis   Rare    
Pericarditis   Extremely rareg    
Thrombophlebitis       Very rare
Constipation   Very common Common
Diarrhea   Rare Common (pea soup)
Bloating with tympany   Very common (84%)[35]    
Diffuse mild abdominal pain   Very common    
Sharp right lower quadrant pain   Rare    
Gastrointestinal hemorrhage   Very rare; usually trace Very common
intestinal perforation       Rare
Hepatosplenomegaly   Common
Jaundice   Common
Gallbladder pain   Very rare
Urinary retention   Common
Hematuria   Rare
Renal pain   Rare
Myalgias Very rare
Arthralgias Very rare
Arthritis (large joint) Extremely rare
Rose spots   Rare
Abscess (anywhere)   Extremely rare Extremely rare Extremely rare
a Very common: Symptoms occur in well over half of cases (approximately 65%-95%).

b Very rare: Symptoms occur in less than 5% of cases.

c Almost all: Symptoms occur in almost all cases.

d Common: Symptoms occur in 35%-65% of cases.

e Rare: Symptoms occur in 5%-35% of cases.

f Blank cells: No mention of the symptom at that phase was found in the literature.

g Extremely rare: Symptoms have been described in occasional case reports.

Table 2. Sensitivities of Cultures [2, 37, 38, 39]
  Incubation Week 1 Week 2 Week 3 Week 4
Bone marrow aspirate (0.5-1 mL)   90% (may decrease after 5 d of antibiotics)
Blood (10-30 mL), stool, or duodenal aspirate culture 40%-80% ~20% Variable (20%-60%)
Urine   25%-30%, timing unpredictable
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