Enteric fever: current issues in effective management and control

Authors

  • Khawaja Shahid Rafi Department of Biology and Immunology, College of Qassim University Medicine, University, Saudi Arabia
  • Tarek Essa Department of Anatomy and Histology, College of Medicine Qassim University, Saudi Arabia
  • Elmuataz E. A. Mohammad Department of Physiology, College of Medicine, Qassim University, Saudi Arabia
  • Mohammad F. Lutfi Department of Physiology, College of Medicine, Qassim University, Saudi Arabia
  • Nagwa Elmustafa Elamin Elbashir Department of Biology and Immunology, College of Qassim University Medicine, University, Saudi Arabia
  • Manal Mohammad Hatem Elhefny Department of Anatomy and Histology, College of Medicine Qassim University, Saudi Arabia
  • Mohammad Hindawy Department of Anatomy and Histology, College of Medicine Qassim University, Saudi Arabia

DOI:

https://doi.org/10.18203/2320-6012.ijrms20251021

Keywords:

Salmonella, Non typhoidal salmonellae, Multidrug resistant strains, ESBL, QRDR strains, Typhoid, Enteric fever

Abstract

Typhoidal salmonella is the causative agent of enteric fever. All are strict human pathogens. It spread through the consumption of contaminated food and water. It presents with high-grade fever, rigors, headache, malaise, some abdominal discomfort, leukopenia, thrombocytopenia, and relative bradycardia/tachycardia. None of them is diagnostic for enteric fever. Antibiotics are the mainstay in the treatment. The management of the disease has become problematic due to the development and spread of MDR genes among the bacterial populations. Efficient laboratory support is required for appropriate antibiotic administration. Among the laboratory tests, the only one to be relied upon for definitive diagnosis is blood or bone marrow culture. It is highly specific, but specificity is low, so a number of false negatives can result. Nucleic acid-based tests are not standardized and are resource-intensive, so they cannot be made available to all patients in all areas. Serological methods also lack standardization, so false positives and negatives cannot be ruled out. Vaccination too does not provide good protection, especially in the adults where it has not been extensively studied. The majority of the patients are treated on clinical suspicion, and antibiotics are administered.

Metrics

Metrics Loading ...

References

Neupane DP, Dulal HP, Song J. Enteric fever diagnosis: current challenges and future directions. Pathogens. 2021;10(4):410. DOI: https://doi.org/10.3390/pathogens10040410

Jeffrey D. Typhoid and paratyphoid collaborators. The global burden of typhoid and paratyphoid fevers: a systematic analysis for the global burden of disease study 2017. Lancet Infect Dis. 2019;19(4):369-81. DOI: https://doi.org/10.1016/S1473-3099(18)30685-6

Kim C, Latif I, Neupane DP, Lee GY, Kwon RS, Batool A, et al. The molecular basis of extensively drug-resistant Salmonella Typhi isolates from pediatric septicemia patients. PLoS One. 2021;16(9):257744. DOI: https://doi.org/10.1371/journal.pone.0257744

Galgallo DA, Roka ZG, Boru WG, Abill K, Ransom J. Investigation of a typhoid fever epidemic in Moyale sub-county, Kenya, 2014–2015. J Health Popul Nutr. 2018;37:14. DOI: https://doi.org/10.1186/s41043-018-0144-2

Kabwama SN, Bulage L, Nsubuga F. A large and persistent outbreak of typhoid fever caused by consuming contaminated water and street-vended bever ages: Kampala, Uganda, January-June 2015. BMC Public Health. 2017;17:23. DOI: https://doi.org/10.1186/s12889-016-4002-0

Abade A, Eidex RB, Maro A, Gratz J, Liu J, Kiwelu I, et al. Use of TaqMan array cards to screen outbreak specimens for causes of febrile illness in Tanzania. Am J Trop Med Hyg. 2018;98:1640–2. DOI: https://doi.org/10.4269/ajtmh.18-0071

Nahimana MR, Ngoc CT, Olu O, Nyamusore J, Isiaka A, Ndahindwa V, et al. A. Knowledge, attitude and practice of hygiene and sanitation in a Burundian refugee camp: implications for control of a Salmonella typhi outbreak. Pan Afr Med J. 2017;28:54. DOI: https://doi.org/10.11604/pamj.2017.28.54.12265

Baker S, Favorov M, Dougan G. Searching for the elusive typhoid diagnostic. BMC Infect Dis. 2010;10:45. DOI: https://doi.org/10.1186/1471-2334-10-45

Brenner FW, Villar RG, Angulo FJ, Tauxe R, Swaminathan B. Salmonella nomenclature. J Clin Microbiol. 2000;38(7):2465-7. DOI: https://doi.org/10.1128/JCM.38.7.2465-2467.2000

Uzzau S, Brown DJ, Wallis T, Rubino S, Leori G, Bernard S, et al. Host adapted serotypes of Salmonella enterica. Epidemiol Infect. 2000;125(2):229-55. DOI: https://doi.org/10.1017/S0950268899004379

Velge P, Cloeckaert A, Barrow P. Emergence of Salmonella epidemics: The problems related to Salmonella enterica serotype Enteritidis and multiple antibiotic resistance in other major serotypes. Vet. Res. 2005;36:267–88. DOI: https://doi.org/10.1051/vetres:2005005

Feasey NA, Dougan G, Kingsley RA, Heyderman RS, Gordon MA. Invasive non-typhoidal salmonella disease: An emerging and neglected tropical disease in Africa. Lancet. 2012;379:2489–99. DOI: https://doi.org/10.1016/S0140-6736(11)61752-2

Ochman H, Groisman EA. Distribution of pathogenicity islands in Salmonella spp Infect. Immun. 1996;64:5410–2. DOI: https://doi.org/10.1128/iai.64.12.5410-5412.1996

Tsui IS, Yip CM, Hackett J, Morris C. The type IVB pili of Salmonella enterica serovar Typhi bind to the cystic fibrosis transmembrane conductance regulator. Infect. Immun. 2003;71:6049–50. DOI: https://doi.org/10.1128/IAI.71.10.6049-6050.2003

Fuentes JA, Villagra N, Castillo-Ruiz M, Mora GC. The Salmonella typhi hlyE gene plays a role in invasion of cultured epithelial cells and its functional transfer to S. Typhimurium promotes deep organ infection in mice. Res. Microbiol. 2008;159:279–87. DOI: https://doi.org/10.1016/j.resmic.2008.02.006

Fowler CC, Chang SJ, Gao X, Geiger T, Stack G, Galan JE. Emerging insights into the biology of typhoid toxin. Curr Opin Microbiol. 2017;35:70–7. DOI: https://doi.org/10.1016/j.mib.2017.01.012

Garai P, Gnanadhas DP, Chakravortty D. Salmonella enterica serovars Typhimurium and Typhi as model organisms: Revealing paradigm of host-pathogen interactions. Virulence 2012;3:377–88. DOI: https://doi.org/10.4161/viru.21087

World Health Organization. (‎2003)‎. Background document: the diagnosis, treatment and prevention of typhoid fever. World Health Organization. Available at: https://iris.who.int/handle. Accessed on 23 November 2024.

Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, et al. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature. 2001;410(6832):1099-103. DOI: https://doi.org/10.1038/35074106

Tötemeyer S, Kaiser P, Maskell DJ, Bryant CE. Sublethal infection of C57BL/6 mice with Salmonella enterica Serovar typhimurium leads to an increase in levels of Toll-like receptor 1 (TLR1), TLR2, and TLR9 mRNA as well as a decrease in levels of TLR6 mRNA in infected organs. Infect Immun. 2005;73(3):1873-8. DOI: https://doi.org/10.1128/IAI.73.3.1873-1878.2005

Hiyoshi H, Wangdi T, Lock G, Saechao C, Raffatellu M, Cobb BA, et al. Mechanisms to evade the phagocyte respiratory burst arose by convergent evolution in Typhoidal Salmonella serovars. Cell Rep. 2018;22(7):1787-97. DOI: https://doi.org/10.1016/j.celrep.2018.01.016

Wangdi T, Lee CY, Spees AM, Yu C, Kingsbury DD, Winter SE, et al. The Vi capsular polysaccharide enables Salmonella enterica Serovar typhi to evade microbe-guided neutrophil chemotaxis. PLoS Pathog. 2014;10(8):1004306. DOI: https://doi.org/10.1371/journal.ppat.1004306

Khan MI, Soofi SB, Ochiai RL, Khan MJ, Sahito SM, Habib MA.et al. Epidemiology, clinical presentation, and patterns of drug resistance of Salmonella Typhi in Karachi, Pakistan. J Infect Dev Ctries. 2012;6(10):704-14. DOI: https://doi.org/10.3855/jidc.1967

Crump JA, Sjölund-Karlsson M, Gordon MA, Parry CM. Epidemiology, clinical presentation, laboratory diagnosis, antimicrobial resistance, and antimicrobial management of invasive salmonella infections. Clin Microbiol Rev. 2015;28(4):901-37. DOI: https://doi.org/10.1128/CMR.00002-15

Crump JA. Typhoid Fever and the challenge of nonmalaria febrile illness in Sub-Saharan Africa Clin Infect Dis. 2012;54:1107–9. DOI: https://doi.org/10.1093/cid/cis024

Parry CM, Hien TT, Dougan G, White NJ, Farrar JJ. Typhoid fever. N Engl J Med. 2002;347(22):1770-82. DOI: https://doi.org/10.1056/NEJMra020201

Maskey AP, Day JN, Phung QT, Thwaites GE, Campbell JI, Zimmerman M., et al Salmonella enterica serovar Paratyphi A and S. enterica serovar Typhi cause indistinguishable clinical syndromes in Kathmandu, Nepal. Clin Infect Dis. 2006;42(9):1247-53. DOI: https://doi.org/10.1086/503033

Sejvar J, Lutterloh E, Naiene J, Likaka A, Manda R, Nygren B, et al. Neurologic manifestations associated with an outbreak of typhoid fever, Malawi--Mozambique, 2009: an epidemiologic investigation. PLoS One. 2012;7(12):46099. DOI: https://doi.org/10.1371/journal.pone.0046099

Holt KE, Phan MD, Baker S, Duy PT, Nga TV, Nair S, et al. Emergence of a globally dominant IncHI1 plasmid type associated with multiple drug-resistant typhoid. PLoS Negl Trop Dis. 2011;5(7):1245. DOI: https://doi.org/10.1371/journal.pntd.0001245

Wong VK, Baker S, Pickard DJ, Parkhill J, Page AJ, Feasey NA, et al. Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events. Nat Genet. 2015;47(6):632-9. DOI: https://doi.org/10.1038/ng.3281

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;39:1571–6. DOI: https://doi.org/10.1128/JCM.39.4.1571-1576.2001

Nizami SQ, Bhutta ZA, Siddiqui AA, Lubbad L. Enhanced detection rate of typhoid fever in children in a periurban slum in Karachi, Pakistan using polymerase chain reaction technology. Scand J Clin Lab Invest. 2006;66(5):429-36. DOI: https://doi.org/10.1080/00365510600791724

Nga TV, Karkey A, Dongol S, Thuy HN, Dunstan S, Holt K., et al. The sensitivity of real-time PCR amplification targeting invasive Salmonella serovars in biological specimens. BMC Infect Dis. 2010;10:125. DOI: https://doi.org/10.1186/1471-2334-10-125

Fadeel MA, House BL, Wasfy MM, et al. Evaluation of a newly developed ELISA against Widal, TUBEX-TF and Typhidot for typhoid fever surveillance. J Infect Dev Ctries. 2011;5(3):169-75. DOI: https://doi.org/10.3855/jidc.1339

Tam FCH, Lim PL. The TUBEXTM typhoid test based on particle-inhibition immunoassay detects IgM but not IgG anti-O9 antibodies. J Immunol Methods. 2003;282 (2):83–91 DOI: https://doi.org/10.1016/j.jim.2003.07.006

Cherian T, Sridharan G, Mohandas V, John TJ. Prevalence of Salmonella typhi O and H antibodies in the serum of infants and preschool children. Indian Pediatr. 1990;27(3):293-4.

Islam K, Sayeed MA, Hossen E, Khanam F, Charles R C, Andrews J. Comparison of the performance of the tptest, tubex, typhidot and widal immunodiagnostic assays and blood cultures in detecting patients with typhoid fever in bangladesh, including using a bayesian latent class modeling approach. PLoS Negl Trop Dis. 2016;10(4):4558. DOI: https://doi.org/10.1371/journal.pntd.0004558

Keddy KH, Sooka A, Letsoalo ME, Hoyland G, Chaignat CL, Morrissey AB, et al. Crump JA. Sensitivity and specificity of typhoid fever rapid antibody tests for laboratory diagnosis at two sub-Saharan African sites. Bull World Health Organ. 2011;89(9):640-7. DOI: https://doi.org/10.2471/BLT.11.087627

Wijedoru L, Mallett S, Parry CM. Rapid diagnostic tests for typhoid and paratyphoid (enteric) fever. Cochrane Database Syst Rev. 2017;5(5):8892. DOI: https://doi.org/10.1002/14651858.CD008892.pub2

Bundalian R Jr, Valenzuela M, Tiongco RE. Achieving accurate laboratory diagnosis of typhoid fever: a review and meta-analysis of TUBEX® TF clinical performance. Pathog Glob Health. 2019;113(7):297-308. DOI: https://doi.org/10.1080/20477724.2019.1695081

Storey HL, Huang Y, Crudder C, Golden A, de los Santos T, Hawkins K. A Meta-Analysis of Typhoid Diagnostic Accuracy Studies: A Recommendation to Adopt a Standardized Composite Reference. PLoS One. 2015;10(11):142364. DOI: https://doi.org/10.1371/journal.pone.0142364

Charles RC, Sheikh A, Krastins B, Harris JB, Bhuiyan MS, LaRocque RC., et al. Characterization of anti-Salmonella enterica serotype Typhi antibody responses in bacteremic Bangladeshi patients by an immunoaffinity proteomics-based technology. Clin Vaccine Immunol. 2010;17(8):1188-95. DOI: https://doi.org/10.1128/CVI.00104-10

Ansong C, Yoon H, Norbeck AD, Gustin JK, McDermott JE, Mottaz HM, et al. Proteomics analysis of the causative agent of typhoid fever. J Proteome Res. 2008;7(2):546-57. DOI: https://doi.org/10.1021/pr070434u

Khanam F, Sheikh A, Sayeed MA, Bhuiyan MS, Choudhury FK, Salma U., et al. Evaluation of a typhoid/paratyphoid diagnostic assay (TPTest) detecting anti-Salmonella IgA in secretions of peripheral blood lymphocytes in patients in Dhaka, Bangladesh. PLoS Negl Trop Dis. 2013;7(7):2316 DOI: https://doi.org/10.1371/journal.pntd.0002316

Sheikh A, Charles RC, Sharmeen N, Rollins SM, Harris JB, Bhuiyan MS, et al. In vivo expression of Salmonella enterica serotype Typhi genes in the blood of patients with typhoid fever in Bangladesh. PLoS Negl Trop Dis. 2011;5(12):1419. DOI: https://doi.org/10.1371/journal.pntd.0001419

Thompson LJ, Dunstan SJ, Dolecek C, Perkins T, House D, Dougan G, et al. Transcriptional response in the peripheral blood of patients infected with Salmonella enterica serovar Typhi. Proc Natl Acad Sci. 2017;5:22433–8. DOI: https://doi.org/10.1073/pnas.0912386106

Blohmke CJ, Muller J, Gibani MM, Dobinson H, Shrestha S, Perinparajah S. Diagnostic host gene signature for distinguishing enteric fever from other febrile diseases. EMBO Mol Med. 2019;11(10):10431. DOI: https://doi.org/10.15252/emmm.201910431

Park KS, Kim H, Kim S, Lee K, Park S, Song J, et al. Nanomagnetic System for Rapid Diagnosis of Acute Infection. ACS Nano. 2017;11(11):11425-32. DOI: https://doi.org/10.1021/acsnano.7b06074

Wain J, Hendriksen RS, Mikoleit ML, Keddy KH, Ochiai RL. Typhoid fever. Lancet. 2015;385(9973):1136-45. DOI: https://doi.org/10.1016/S0140-6736(13)62708-7

Bhutta ZA. Current concepts in the diagnosis and treatment of typhoid fever. BMJ. 2006;333:78–82. DOI: https://doi.org/10.1136/bmj.333.7558.78

Anjum P, Qureshi AH, Rafi S. Fluroquinolone resistance in typhoidal Salmonella and its detection by nalidixic acid disc diffusion. J Pak Med Assoc. 2004;54(6):295-301.

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. Antimicrobe Agents Chemother. 2007;51(12):4315-23. DOI: https://doi.org/10.1128/AAC.00294-07

Koirala KD, Thanh DP, Thapa SD, Arjyal A, Karkey A, Dongol S, et al. Highly resistant Salmonella enterica serovar Typhi with a novel gyrA mutation raises questions about the long-term efficacy of older fluoroquinolones for treating typhoid fever. Antimicrob Agents Chemother. 2012;56(5):2761-2. DOI: https://doi.org/10.1128/AAC.06414-11

Qamar FN, Azmatullah A, Kazi AM, Khan E, Zaidi AK. A three-year review of antimicrobial resistance of Salmonella enterica serovars Typhi and Paratyphi A in Pakistan. J Infect Dev Ctries. 2014;8(8):981-6. DOI: https://doi.org/10.3855/jidc.3817

Patel SR, Bharti S, Pratap CB, Nath G. Drug resistance pattern in the recent isolates of Salmonella Typhi with special reference to cephalosporins and azithromycin in the Gangetic plain. J Clin Diagn Res. 2017;11:1-3. DOI: https://doi.org/10.7860/JCDR/2017/23330.9973

Al Naiemi N, Zwart B, Rijnsburger MC, Roosendaal R, Debets-Ossenkopp YJ, Mulder JA, et al. Extended-spectrum-beta-lactamase production in a Salmonella enterica serotype Typhi strain from the Philippines. J Clin Microbiol. 2008;46(8):2794-5. DOI: https://doi.org/10.1128/JCM.00676-08

Dolecek C, Tran TP, Nguyen NR, Le TP, Ha V, Phung QT., et al., A multi-center randomised controlled trial of gatifloxacin versus azithromycin for the treatment of uncomplicated typhoid fever in children and adults in Vietnam. PLoS One. 2008;3(5):2188. DOI: https://doi.org/10.1371/journal.pone.0002188

Manesh A, Balaji V, Kumar DR, Rupali P. A case of clinical and microbiological failure of azithromycin therapy in Salmonella enterica serotype Typhi despite low azithromycin MIC. Int J Infect Dis. 2017;54:62-3. DOI: https://doi.org/10.1016/j.ijid.2016.11.409

Capoor MR, Nair D, Posti J, Singhal S, Deb M, Aggarwal P, et al. Minimum inhibitory concentration of carbapenems and tigecycline against Salmonella spp. J Med Microbiol. 2009;58(3):337-41. DOI: https://doi.org/10.1099/jmm.0.47853-0

Morosini MI, García-Castillo M, Coque TM, Valverde A, Novais A, Loza E., et al. Antibiotic resistance in extended-spectrum-beta-lactamase-producing Enterobacteriaceae and in vitro activity of tigecycline. Antimicrob Agents Chemother. 2006;50(8):2695-9. DOI: https://doi.org/10.1128/AAC.00155-06

Karki M, Pandit S, Baker S, Basnyat B. Cotrimoxazole treats fluoroquinolone-resistant Salmonella typhi H58 infection. BMJ Case Rep. 2016:21:7223. DOI: https://doi.org/10.1136/bcr-2016-217223

Ramesh U, Das S, Balasubramanian A. Re-emergence of chloramphenicol susceptible Salmonella Typhi and paratyphi a strains in India. Indian J Med Microbiol. 2016;34:262–3. DOI: https://doi.org/10.4103/0255-0857.180393

Pokharel S, Basnyat B, Arjyal A, Mahat SP, Kc RK, Bhuju A, et al. Co-trimoxazole versus azithromycin for the treatment of undifferentiated febrile illness in Nepal: study protocol for a randomized controlled trial. Trials. 2017;18(1):450. DOI: https://doi.org/10.1186/s13063-017-2199-6

Milligan R, Paul M, Richardson M, Neuberger A. Vaccines for preventing typhoid fever. Cochrane Database Syst Rev. 2018;5(5):1261. DOI: https://doi.org/10.1002/14651858.CD001261.pub4

Downloads

Published

2025-04-04

How to Cite

Rafi, K. S., Essa, T., Mohammad, E. E. A., Lutfi, M. F., Elbashir, N. E. E., Elhefny, M. M. H., & Hindawy, M. (2025). Enteric fever: current issues in effective management and control. International Journal of Research in Medical Sciences, 13(5), 2241–2250. https://doi.org/10.18203/2320-6012.ijrms20251021

Issue

Section

Review Articles