Typhoid Fever in Indonesia: Pitfalls in the Diagnosis of Typhoid Fever
Keywords:
Typhoid Fever, diagnostic, Salmonella, Salmonella TyphiAbstract
Typhoid fever remains a major public health issue in Indonesia, with its true burden likely underreported due to diagnostic challenges. The clinical manifestations of typhoid fever are often nonspecific and overlap with other endemic febrile illnesses such as dengue, leptospirosis, and rickettsial infections, leading to frequent misdiagnosis. Although blood culture and PCR are the gold standards, their limited accessibility in Indonesia has resulted in reliance on suboptimal diagnostic tools such as the Widal test and TUBEX TF. Recent advances, including the Nelwan Score and CRP-based differentiation, have shown promise in improving early clinical screening. Furthermore, antibody-based proteomic diagnostics offer enhanced accuracy but remain largely confined to research settings. A combined approach utilizing validated clinical scores, affordable biomarkers, and selective use of serological tests is essential to improve diagnostic accuracy and patient care. Misdiagnosis not only endangers patient outcomes but also contributes to inappropriate antibiotic use, accelerating the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Salmonella Typhi. Resistance to first-line antibiotics and fluoroquinolones has been increasingly reported in Indonesia, although some regions still demonstrate preserved susceptibility. Cautious and evidence-based antibiotic prescribing is therefore critical to mitigating resistance. This article underscores the urgent need to strengthen diagnostic strategies and antimicrobial stewardship to address the persistent challenge of typhoid fever in Indonesia.References
Hancuh M. typhoid fever surveillance, incidence estimates, and progress toward typhoid conjugate vaccine introduction - worldwide, 2018-2022. MMWR Morb Mortal Wkly Rep. 2023;72(7):171-6. doi: 10.15585/mmwr.mm7207a2.
Buckle GC, Walker CL, Black RE. Typhoid fever and paratyphoid fever: Systematic review to estimate global morbidity and mortality for 2010. J Glob Health. 2012 Jun;2(1):010401. doi: 10.7189/jogh.02.010401.
Nurmawati S. Clinical characteristics of enteric fever and performance of the TUBEX TF IgM test in Indonesian hospitals. PLoS Negl Trop Dis. 2024;18(7):e0011848. doi: 10.1371/journal.pntd.0011848.
Jamil KF. The comparison of the clinical symptoms of typhoid fever in adult patients (Tubex vs Widal) in Banda Aceh, Aceh Province, Indonesia. Tropical Medicine Journal. 2017;4(1).
Mauliza, Fitriany J. Typhoid fever profiles at Cut Meutia Hospital, North Aceh, Indonesia, in 2016-2017. Emerald Reach Proceedings Series. 2018 May 4;395–400. doi:10.1108/978-1-78756-793-1-00031.
Kurniawati H, Marianti. Quantitative antibiotic use profile in typhoid. Sriwijaya Journal of Medicine. 2020 Oct 27;3(3):113–8. doi:10.32539/sjm.v3i3.219
Nelwan EJ. Validation of the Nelwan score as a screening tool for the diagnosis of typhoid fever in adults in Indonesia. PLoS One. 2023 May 12;18(5):e0256508. doi: 10.1371/journal.pone.0256508.
Gasem MH. An observational prospective cohort study of the epidemiology of hospitalized patients with acute febrile illness in Indonesia. PLoS Negl Trop Dis. 2020 Jan 10;14(1):e0007927. Doi: 10.1371/journal.pntd.0007927.
Farrar J, Hotez PJ, Junghanss T, et al. Manson’s tropical diseases. Philadelphia, PA: Elsevier; 2024.
Lamy B, Dargère S, Arendrup MC, Parienti J-J, Tattevin P. How to optimize the use of blood cultures for the diagnosis of bloodstream infections? A state-of-the-art. Frontiers in Microbiology. 2016 May 12;7. doi:10.3389/fmicb.2016.00697.
Southeast Asia Infectious Disease Clinical Research Network. Causes and outcomes of sepsis in Southeast Asia: a multinational multicentre cross-sectional study. Lancet Glob Health. 2017 Feb;5(2):e157-e167. doi: 10.1016/S2214-109X(17)30007-4.
Zaranggi A, Fauziah PN, Widhyasih RM. Gambaran hasil pemeriksaan penderita demam tifoid dengan metode Widal di Laboratorium Kesehatan Daerah Kota Sukabumi. J Ilm Kesehat. 2024;16(2):348-55.
Najib MA. Performance of immunodiagnostic tests for typhoid fever: A systematic review and meta-analysis. Pathogens. 2021 Sep 13;10(9):1184. doi: 10.3390/pathogens10091184.
Dyson ZA, Klemm EJ, Palmer S, Dougan G. Antibiotic resistance and typhoid. Clin Infect Dis. 2019 Mar 7;68(Suppl 2):S165-S170. Doi: 10.1093/cid/ciy1111. PMID: 30845331; PMCID: PMC6405283.
Hardjo LNP, Cucunawangsih. Antimicrobial resistance of salmonella enterica serovars typhi and paratyphi isolates from a General Hospital in Karawaci, Tangerang, Indonesia: A Five-Year Review. Int J Microbiol. 2017;2017:6215136. doi: 10.1155/2017/6215136.
Erald GHS, Wardana KDPK, Ivanka D. Epidemiologi dan resistensi antibiotik salmonella typhi dan paratyphi a pada kasus demam tifoid di Jakarta: A systematic literature review. Jurnal Ilmu Psikologi Dan Kesehatan (SIKONTAN). 2023;2(2):173–84.
Kaluse PS, Bhatt N, Bankar N. Study of typhoid fever: A review. Journal of Pharmaceutical Research International. doi:10.9734/jpri/2021/v33i39a32172 2021 Jul 31;286–91.
Haq SA, Alam MN, Hossain SM, Ahmed T, Tahir M. Value of clinical features in the diagnosis of enteric fever. Bangladesh Med Res Counc Bull. 1997; 23(2):42-6.
Basnyat B, Qamar FN, Rupali P, Ahmed T, Parry CM. Enteric fever. BMJ. 2021 Feb 26; doi:10.1136/bmj.n437
Azmatullah A, Qamar FN, Thaver D, Zaidi AK, Bhutta ZA. Systematic review of the global epidemiology, clinical and laboratory profile of enteric fever. J Glob Health. 2015 Dec;5(2):020407. doi: 10.7189/jogh.05.020407.
Bhandari J, Thada PK, Hashmi MF, et al. Typhoid fever. [Updated 2024 Apr 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557513/
Ahmedullah H. Epidemiological and clinical features of Salmonella typhi infection among adult patients in Qatar: A hospital-based study. Oman Med J. 2018;33:468–72.
Marchello CS, Birkhold M, Crump JA. Complications and mortality of typhoid fever: A global systematic review and meta-analysis. J Infect. 2020 Dec;81(6):902-10. doi: 10.1016/j.jinf.2020.10.030. Epub 2020 Nov 2.
Mehndiratta S. Typhoid fever with acute abdominal pain masquerading as a surgical emergency. International Journal of Advanced Medical and Health Research. 2016;3(1):31. doi:10.4103/2350-0298.184673
Sartori DJ, Sun K, Hopkins MA, Sloane MF. Typhoid fever and acute appendicitis: A rare association not yet fully formed. Case Rep Gastroenterol. 2017 Aug 8;11(2):446-451. doi: 10.1159/000479310.
Gomes R. Acute Pancreatitis and Pulmonary Hypertension: Unusual manifestations of typhoid fever. 2020;05(9):241-243.
Khan FY, Elouzi EB, Asif M. Acute acalculous cholecystitis complicating typhoid fever in an adult patient: A case report and review of the literature. Travel Medicine and Infectious Disease. 2009 Jul;7(4):203–6. doi:10.1016/j.tmaid.2009.05.006.
Arfijanto MV, Rindryastuti I. A patient with typhoid hepatitis. The Indonesian Journal of Gastroenterology, Hepatology, and Digestive Endoscopy. 2021 Sept 27;22(2):154–8. doi:10.24871/2222021154-158
Khan M. Typhoid fever complicated by acute renal failure and hepatitis: Case reports and Review. The American Journal of Gastroenterology. 1998 Jun;93(6):1001–3. doi:10.1016/s0002-9270(98)00179-8
Cho JH. Successful endoscopic hemoclipping and conservative management for typhoid fever complicated by massive intestinal bleeding and acute pancreatitis. Medicine. 2019 Aug;98(31). doi:10.1097/md.0000000000016521
Khanam F. Case report: Typhoid fever complicated by ileal perforation in an urban slum of Dhaka, Bangladesh. Am J Trop Med Hyg. 2021 Mar 22;104(5):1755-7. doi: 10.4269/ajtmh.20-1448
Sharma AM, Sharma OP. Pulmonary manifestations of typhoid fever. Chest. 1992 Apr;101(4):1144–6. doi:10.1378/chest.101.4.1144
Khan FY, Habas EM, Akbar RA, Sulaiman TO. A fatal typhoid acute respiratory distress syndrome. Saudi Journal for Health Sciences. 2021 Sept;10(3):209–11. doi:10.4103/sjhs.sjhs_117_21
Alam A. Unusual presentation of typhoid encephalopathy: Case reports. 2023 Sept 27; doi:10.21203/rs.3.rs-3330156/v1
Esa H, Norazlah B, Hameed AA, Ding CH, Wahab AA. Typhoid fever presenting as acute psychosis in a young adult: case report and literature review of typhoid psychosis. Trop Biomed. 2021 Jun 1;38(2):192-195. doi: 10.47665/tb. 38.2.057.
Sejvar J. Neurologic manifestations associated with an outbreak of typhoid fever, Malawi--Mozambique, 2009: An epidemiologic investigation. PLoS One. 2012;7(12):e46099. doi: 10.1371/journal.pone.0046099.
Javad Kv M, Saif M, Kalathil B, Mohamed F, Uvais NA. Sensorineural hearing loss as an atypical presentation of typhoid fever: A case report. Trop Doct. 2024 Apr;54(2):189-90. doi: 10.1177/00494755241229752.
Yashodhara BM, Yousuf UA. A case report of typhoid fever masquerading as acute typhoid glomerulonephritis. International Journal of Case Reports and Images. 2011;2(3):1. doi:10.5348/ijcri-2011-03-21-cr-1
World Health Organization. Background document: the diagnosis, treatment, and prevention of typhoid fever. 2003. http://www.who.int/iris/handle/10665/68122.
Prakash P, Mishra OP, Singh AK, Gulati AK, Nath G. Evaluation of nested PCR in diagnosis of typhoid fever. J Clin Microbiol. 2005 Jan;43(1):431-2. doi: 10.1128/JCM.43.1.431-432.2005.
Pohan HT. Clinical and laboratory manifestations of typhoid fever at Persahabatan Hospital, Jakarta. Acta Med Indones. 2004;36(2):78-83. PMID: 15673941.
Idhayu AT, Chen LK, Suhendro S. The difference of C-reactive protein levels in acute fever caused by dengue and typhoid infections. J Penyakit Dalam Indones. 2016;3(3):105–9. doi:10.7454/jpdi.v3i3.24
Darton TC, Baker S, Randall A, et al. Identification of novel serodiagnostic signatures of typhoid fever using a Salmonella proteome array. Front Microbiol. 2017;8:1794. doi:10.3389/fmicb.2017.01794
Liang L, Juarez S, Nga TVT, et al. Immune profiling with a Salmonella Typhi antigen microarray identifies new diagnostic biomarkers of human typhoid. Sci Rep. 2013;3:1043. doi:10.1038/srep01043
Brunette GW. CDC Yellow book 2018: Health information for international travel. New York: Oxford University Press; 2017.
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; 28:901–37.
Antillon M, Saad NJ, Baker S, Pollard AJ, Pitzer VE. The relationship between blood sample volume and diagnostic sensitivity of blood culture for typhoid and paratyphoid fever: A systematic review and meta-analysis. J Infect Dis. 2018 Nov 10;218(suppl.4): S255-S267. doi: 10.1093/infdis/jiy471
Diwaker A, Tiwari A, Jain S, et al. Enteric fever and the diagnostic tools: Defining the accuracy. Frontiers in Bacteriology. 2024 Jan 29;3. doi:10.3389/fbrio.2024.1332180
Zhou L, Pollard AJ. A fast and highly sensitive blood culture PCR method for clinical detection of Salmonella enterica serovar Typhi. Ann Clin Microbiol Antimicrob. 2010 Apr 19;9:14. Doi: 10.1186/1476-0711-9-14.
Von KV, Konings F, Aaby P, et al. The typhoid fever surveillance in Africa Program (TSAP): Clinical, diagnostic, and epidemiological methodologies. Clinical Infectious Diseases. 2016 Mar 1;62(suppl 1). doi:10.1093/cid/civ693
Darton TC. Blood culture-PCR to optimise typhoid fever diagnosis after controlled human infection identifies frequent asymptomatic cases and evidence of primary bacteraemia. J Infect. 2017 Apr;74(4):358-66. doi: 10.1016/j.jinf.2017.01.006.
Mohapatro A, Mahendran SK, Das TK. Clinical decision support system for the detection of dengue. Journal of Cases on Information Technology. 2021 Oct 15;23(4):1–29. doi:10.4018/jcit 289649
Kirti N, S. Krishna S, Shukla D. Salmonella infections: An update, detection and control strategies. Salmonella - Current Trends and Perspectives in Detection and Control. 2024; doi:10.5772/intechopen.1004835
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: 10.1080/20477724.2019.1695081.
Naheed A, Ram PK, Brooks WA, et al. Clinical value of Tubex and Typhidot rapid diagnostic tests for typhoid fever in an urban community clinic in Bangladesh. Diagn Microbiol Infect Dis. 2008;61(4):381–6. doi:10.1016/j.diagmicrobio.2008.03.018
Marsela H, Setiabudi D, Indrati AR. Validity of immunoglobulin M anti-Salmonella typhi serologic test in childhood typhoid fever. Althea Medical Journal. 2017;4(1):138–42. doi:10.15850/amj.v4n1.1035
Adhikari A, Rauniyar R, Raut PP, Manandhar KD, Gupta BP. Evaluation of the sensitivity and specificity of ELISA against the Widal test for typhoid diagnosis in the endemic population of Kathmandu. BMC Infect Dis. 2015 Nov 14;15:523. Doi: 10.1186/s12879-015-1248-6.
Mawazo A, Bwire GM, Matee MIN. Performance of Widal test and stool culture in the diagnosis of typhoid fever among suspected patients in Dar es Salaam, Tanzania. BMC Res Notes. 2019;12(1):316. doi: 10.1186/s13104-019-4340-y.
Pouzol S, Tanmoy AM, Ahmed D, et al. Clinical Evaluation of a multiplex pcr for the detection of Salmonella enterica serovars typhi and paratyphi a from blood specimens in a high-endemic setting. Am J Trop Med Hyg. 2019;101(3):513-20. doi: 10.4269/ajtmh.18-0992
Handojo I, Dewi R. The diagnostic value of the ELISA-Ty test for the detection of typhoid fever in children. Southeast Asian J Trop Med Public Health. 2000 Dec;31(4):702-7.
Getahun SA. Assessment of rapid diagnostic tests for typhoid diagnosis and assessment of febrile illness outbreaks in Fiji. Am J Trop Med Hyg. 2021 Nov 29;106(2):543-9. doi: 10.4269/ajtmh.21-0771.
Bhalerao U, Preethi L, Bhukya PL, Mhaske ST. Dengue haemorrhagic fever: A resurgent arbovirosis in humans. Emerging Human Viral Diseases. 2023;I:315–43. doi:10.1007/978-981-99-2820-0_12
Snowden J, Ladd M, King KC. Rickettsial infection. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK431127/
Wang S, Dunn N. Leptospirosis. [Updated 2024 Sep 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441858/
Setiati S, Alwi I, Sudoyo AW, Stiyohadi B, Syam AF. Buku ajar ilmu penyakit dalam. Jilid I. 6th ed. Jakarta: InternaPublishing; 2014.
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. doi: 10.1093/clinids/4.2.551.
Mutai WC, Muigai AWT, Waiyaki P, Kariuki S. Multi-drug resistant Salmonella enterica serovar Typhi isolates with reduced susceptibility to ciprofloxacin in Kenya. BMC Microbiol. 2018 Nov 14;18(1):187. doi: 10.1186/s12866-018-1332 3.
Tristianti IZ, Dewi LM. Comparison of sensitivity and resistance to Ceftriaxone with Chloramphenicol in the treatment of Salmonella typhi infection: Literature review. Proceeding ISETH (International Summit on Science, Technology, and Humanity). 2021;62-71.
Veeraraghavan B, Pragasam AK, Bakthavatchalam YD, Ralph R. Typhoid fever: issues in laboratory detection, treatment options & concerns in management in developing countries. Future Sci OA. 2018 Jul;4(6):FSO312.
Moehario LH, Robertus T, Tjoa E, D. Gunardi W, Nusatia ACh, Edbert D. Antibiotic susceptibility patterns of Salmonella typhi in Jakarta and its trends within the past decade. Journal of Biological Sciences. 2018 Dec 15;19(1):40–5. doi:10.3923/jbs.2019.40.45.
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