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Typhoid Fever Medication

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

Antibiotics

Class Summary

Definitive treatment of typhoid fever (enteric fever) is based on susceptibility. As a general principle of antimicrobial treatment, intermediate susceptibility should be regarded as equivalent to resistance. Between 1999 and 2006, 13% of S typhi isolates collected in the United States were multidrug resistant.

Until susceptibilities are determined, antibiotics should be empiric, for which there are various recommendations. The authors of this article recommend combination treatment with ceftriaxone and ciprofloxacin when neither the sensitivities nor the geographical origin of the bacteria is known.

The particular sensitivity pattern of the organism in its area of acquisition should be the major basis of empiric antibiotic choice. It may soon become necessary to treat all cases presumptively for multidrug resistance until sensitivities are obtained.

History of antibiotic resistance

Chloramphenicol was used universally to treat typhoid fever from 1948 until the 1970s, when widespread resistance occurred. Ampicillin and trimethoprim-sulfamethoxazole (TMP-SMZ) then became treatments of choice. However, in the late 1980s, some S typhi and S paratyphi strains (multidrug resistant [MDR] S typhi or S paratyphi) developed simultaneous plasmid-mediated resistance to all three of these agents.

Fluoroquinolones are highly effective against susceptible organisms, yielding a better cure rate than cephalosporins. Unfortunately, resistance to first-generation fluoroquinolones is widespread in many parts of Asia.

In recent years, third-generation cephalosporins have been used in regions with high fluoroquinolone resistance rates, particularly in south Asia and Vietnam. Unfortunately, sporadic resistance has been reported, so it is expected that these will become less useful over time.[44]

Mechanisms of antibiotic resistance

The genes for antibiotic resistance in S typhi and S paratyphi are acquired from Escherichia coli and other gram-negative bacteria via plasmids. The plasmids contain cassettes of resistance genes that are incorporated into a region of the Salmonella genome called an integron. Some plasmids carry multiple cassettes and immediately confer resistance to multiple classes of antibiotics. This explains the sudden appearance of MDR strains of S typhi and S paratyphi, often without intermediate strains that have less-extensive resistance.

The initial strains of antibiotic-resistant S typhi and S paratyphi carried chloramphenicol acetyltransferase type I, which encodes an enzyme that inactivates chloramphenicol via acetylation. MDR strains may carry dihydrofolate reductase type VII, which confers resistance to trimethoprim. Interestingly, in areas where these drugs have fallen out of use, S typhi has reverted to wild type, and they are often more effective than newer agents.[45, 46, 47, 35]

Resistance to fluoroquinolones is evolving in an ominous direction. Fluoroquinolones target DNA gyrase and topoisomerase IV, bacterial enzymes that are part of a complex that uncoils and recoils bacterial DNA for transcription.[48] S typhi most commonly develops fluoroquinolone resistance through specific mutations in gyrA and parC, which code for the binding region of DNA gyrase and topoisomerase IV, respectively.

A single point mutation gyrA confers partial resistance. If a second gyrA point mutation is added, the resistance increases somewhat. However, a mutation in parC added to a single gyrA mutation confers full in vitro resistance to first-generation fluoroquinolones. Clinically, these resistant strains show a 36% failure rate when treated with a first-generation fluoroquinolone such as ciprofloxacin.[49] The risk of relapse after bacterial clearance is higher in both partially and fully resistant strains than in fully susceptible strains.[23]

The third-generation fluoroquinolone gatifloxacin appears to be highly effective against all known clinical strains of S typhi both in vitro and in vivo. due to its unique interface with gyrA. It achieves better results than cephalosporins even among strains that are considered fluoroquinolone resistant. However, gatifloxacin is no longer on the market in the United States, and its use cannot be generalized to any other member of the class.[50, 51]

In any case, as gatifloxacin replaces older fluoroquinolones in high-prevalence resistance is bound to emerge. Any two of a number of gyrA mutations, when added to the parC mutation, confer full in vitro resistance. Although such a combination has yet to be discovered in vivo, all of these mutations exist in various clinic strains, and it seems highly likely that a gatifloxacin-resistant one will be encountered clinically if selective pressure with fluoroquinolones continues to be exerted.[49]

Geography of resistance

Among S typhi isolates obtained in the United States between 1999 and 2006, 43% were resistant to at least one antibiotic.

Nearly half of S typhi isolates found in the United States now come from travelers to the Indian subcontinent, where fluoroquinolone resistance is endemic (see Table 3). The rate of fluoroquinolone resistance in south and Southeast Asia and, to some extent, in East Asia is generally high and rising (see Table 3). Susceptibility to chloramphenicol, TMP-SMZ, and ampicillin in South Asia is rebounding. In Southeast Asia, MDR strains remain predominant, and some acquired resistance to fluoroquinolones by the early 2000s.

The most recent professional guideline for the treatment of typhoid fever in south Asia was issued by the Indian Association of Pediatrics (IAP) in October 2006. Although these guidelines were published for pediatric typhoid fever, the authors feel that they are also applicable to adult cases. For empiric treatment of uncomplicated typhoid fever, the IAP recommends cefixime and, as a second-line agent, azithromycin. For complicated typhoid fever, they recommend ceftriaxone. Aztreonam and imipenem are second-line agents for complicated cases.[52] The authors believe that the IAP recommendations apply to empiric treatments of typhoid fever in both adults and children.

In high-prevalence areas outside the areas discussed above, the rate of intermediate sensitivity or resistance to fluoroquinolones is 3.7% in the Americas (P =.132), 4.7% (P =.144) in sub-Saharan Africa, and 10.8% (P =.706) in the Middle East. Therefore, for strains that originate outside of south or Southeast Asia, the WHO recommendations may still be valid—that uncomplicated disease should be treated empirically with oral ciprofloxacin and complicated typhoid fever from these regions should be treated with intravenous ciprofloxacin.[44, 47, 53, 24, 54]

Resistance in the United States

In the United States in 2012, 68% of S typhi isolates and 95% of S paratyphi isolates were fully resistant to nalidixic acid. While full resistance to ciprofloxacin was considerably less, intermediate susceptibilities to ciprofloxacin in both organisms closely matched resistance to nalidixic acid. Note that nalidixic acid is a nontherapeutic drug that is used outside of the United States as a stand-in for fluoroquinolones in sensitivity assays. In the United States, it is still used specifically for S typhi infection.[44, 22]

The rate of multidrug resistance in 2012 was 9% in S typhi and 0% in S paratyphi. (Multidrug-resistant S typhi is, by definition, resistant to the original first-line agents, ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole.)

There have been no cases of ceftriaxone-resistant S typhi or S paratyphi documented in the United States, at least since 2003.[55]

Antibiotic resistance is a moving target. Reports are quickly outdated, and surveys of resistance may have limited geographic scope. Therefore, any recommendation regarding antibiotic treatment must be taken with a grain of salt. However, in the authors' opinion, if the origin of the infection is unknown, the combination of a first-generation fluoroquinolone and a third-generation cephalosporin should be used. This allows for most effective clearance if the organism is fluoroquinolone-susceptible but still covers strains that are not.

Table 3. Antibiotic Recommendations by Origin and Severity

Location

Severity

First-Line Antibiotics

Second-Line Antibiotics

South Asia, East Asia[52]

[56, 45]

Uncomplicated

Cefixime PO

Azithromycin PO

Complicated

Ceftriaxone IV or

Cefotaxime IV

Aztreonam IV or

Imipenem IV

Eastern Europe, Middle East, sub-Saharan Africa, South America[53, 57]

Uncomplicated

Ciprofloxacin PO or

Ofloxacin PO

Cefixime PO or

Amoxicillin PO or

TMP-SMZ PO

or Azithromycin PO

Complicated

Ciprofloxacin IV or

Ofloxacin IV

Ceftriaxone IV or

Cefotaxime IV or

Ampicillin IV

or

TMP-SMZ IV

Unknown geographic origin or Southeast Asia[58, 52]

[56, 45, 53, 57]

Uncomplicated

Cefixime PO plus

Ciprofloxacin PO or

Ofloxacin PO

Azithromycin PO*

Complicated

Ceftriaxone IV or

Cefotaxime IV, plus

Ciprofloxacin IV or

Ofloxacin IV

Aztreonam IV or

Imipenem IV, plus

Ciprofloxacin IV

or

Ofloxacin IV

*Note that the combination of azithromycin and fluoroquinolones is not recommended because it may cause QT prolongation and is relatively contraindicated.

Future directions

A meta-analysis found that azithromycin appeared to be superior to fluoroquinolones and ceftriaxone with lower rates of clinical failure and relapse respectively. Although the data did not permit firm conclusions, if further studies confirm the trend, azithromycin could become a first-line treatment.[59]

Chloramphenicol (Chloromycetin)

 

Binds to 50S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria. Since its introduction in 1948, has proven to be remarkably effective for enteric fever worldwide. For sensitive strains, still most widely used antibiotic to treat typhoid fever. In the 1960s, S typh i strains with plasmid-mediated resistance to chloramphenicol began to appear and later became widespread in many endemic countries of the Americas and Southeast Asia, highlighting need for alternative agents.

Produces rapid improvement in patient's general condition, followed by defervescence in 3-5 d. Reduced preantibiotic-era case-fatality rates from 10%-15% to 1%-4%. Cures approximately 90% of patients. Administered PO unless patient is nauseous or experiencing diarrhea; in such cases, IV route should be used initially. IM route should be avoided because it may result in unsatisfactory blood levels, delaying defervescence.

Amoxicillin (Trimox, Amoxil, Biomox)

 

Interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria. At least as effective as chloramphenicol in rapidity of defervescence and relapse rate. Convalescence carriage occurs less commonly than with other agents when organisms are fully susceptible. Usually given PO with a daily dose of 75-100 mg/kg tid for 14 d.

Trimethoprim and sulfamethoxazole (Bactrim DS, Septra)

 

Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Antibacterial activity of TMP-SMZ includes common urinary tract pathogens, except Pseudomonas aeruginosa. As effective as chloramphenicol in defervescence and relapse rate. Trimethoprim alone has been effective in small groups of patients.

Ciprofloxacin (Cipro)

 

Fluoroquinolone with activity against pseudomonads, streptococci, MRSA, Staphylococcus epidermidis, and most gram-negative organisms but no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth. Continue treatment for at least 2 d (7-14 d typical) after signs and symptoms have disappeared. Proven to be highly effective for typhoid and paratyphoid fevers. Defervescence occurs in 3-5 d, and convalescent carriage and relapses are rare. Other quinolones (eg, ofloxacin, norfloxacin, pefloxacin) usually are effective. If vomiting or diarrhea is present, should be given IV. Fluoroquinolones are highly effective against multiresistant strains and have intracellular antibacterial activity.

Not currently recommended for use in children and pregnant women because of observed potential for causing cartilage damage in growing animals. However, arthropathy has not been reported in children following use of nalidixic acid (an earlier quinolone known to produce similar joint damage in young animals) or in children with cystic fibrosis, despite high-dose treatment.

Cefotaxime (Claforan)

 

Arrests bacterial cell wall synthesis, which inhibits bacterial growth. Third-generation cephalosporin with gram-negative spectrum. Lower efficacy against gram-positive organisms. Excellent in vitro activity against S typhi and other salmonellae and has acceptable efficacy in typhoid fever. Only IV formulations are available. Recently, emergence of domestically acquired ceftriaxone-resistant Salmonella infections has been described.

Azithromycin (Zithromax)

 

Treats mild to moderate microbial infections. Administered PO at 10 mg/kg/d (not exceeding 500 mg), appears to be effective to treat uncomplicated typhoid fever in children 4-17 y. Confirmation of these results could provide an alternative for treatment of typhoid fever in children in developing countries, where medical resources are scarce.

Ceftriaxone (Rocephin)

 

Third-generation cephalosporin with broad-spectrum gram-negative activity against gram-positive organisms; Excellent in vitro activity against S typhi and other salmonellae.

Cefoperazone (Cefobid)

 

Discontinued in the United States. Third-generation cephalosporin with gram-negative spectrum. Lower efficacy against gram-positive organisms.

Ofloxacin (Floxin)

 

A pyridine carboxylic acid derivative with broad-spectrum bactericidal effect.

Levofloxacin (Levaquin)

 

For pseudomonal infections and infections due to multidrug-resistant gram-negative organisms.

Next

Corticosteroids

Class Summary

Dexamethasone may decrease the likelihood of mortality in severe typhoid fever cases complicated by delirium, obtundation, stupor, coma, or shock if bacterial meningitis has been definitively ruled out by cerebrospinal fluid studies. To date, the most systematic trial of this has been a randomized controlled study in patients aged 3-56 years with severe typhoid fever who were receiving chloramphenicol therapy. This study compared outcomes in 18 patients given placebo with outcomes in 20 patients given dexamethasone 3 mg/kg IV over 30 minutes followed by dexamethasone 1 mg/kg every 6 hours for 8 doses. The fatality rate in the dexamethasone arm was 10% versus 55.6% in the placebo arm (P =.003).[60]

Nonetheless, this point is still debated. A 2003 WHO statement endorsed the use of steroids as described above, but reviews by eminent authors in the New England Journal of Medicine (2002)[4] and the British Medical Journal (2006)[61] do not refer to steroids at all. A 1991 trial compared patients treated with 12 doses of dexamethasone 400 mg or 100 mg to a retrospective cohort in whom steroids were not administered. This trial found no difference in outcomes among the groups.[62]

The data are sparse, but the authors of this article agree with the WHO that dexamethasone should be used in cases of severe typhoid fever.

Dexamethasone (Decadron)

 

Prompt administration of high-dose dexamethasone reduces mortality in patients with severe typhoid fever without increasing incidence of complications, carrier states, or relapse among survivors.

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Contributor Information and Disclosures
Author

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.

Coauthor(s)

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.

References
  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 www.who.int/vaccines-documents/.

  55. National Antimicrobial Resistance Monitoring System 2012 Human Isolates Final Report. Available at http://www.cdc.gov/narms/pdf/2012-annual-report-narms-508c.pdf.

  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].

 
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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
Neurologic
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        
Pulmonary
Mild cough   Common    
Bronchitic cough   Common    
Rales   Common    
Pneumonia   Rare (lobar) Rare Common



(basal)



Cardiovascular
Dicrotic pulse   Rare Common
Myocarditis   Rare    
Pericarditis   Extremely rareg    
Thrombophlebitis       Very rare
Gastrointestinal
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
Urogenital
Urinary retention   Common
Hematuria   Rare
Renal pain   Rare
Musculoskeletal
Myalgias Very rare
Arthralgias Very rare
Rheumatologic
Arthritis (large joint) Extremely rare
Dermatologic
Rose spots   Rare
Miscellaneous
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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