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Zotero
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Etiologies of Acute Undifferentiated Febrile Illness in Bangkok, Thailand
Viravarn Luvira
Viravarn Luvira
Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;
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Udomsak Silachamroon
Udomsak Silachamroon
Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;
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Watcharapong Piyaphanee
Watcharapong Piyaphanee
Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;
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Saranath Lawpoolsri
Saranath Lawpoolsri
Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;
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Wirongrong Chierakul
Wirongrong Chierakul
Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;
Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;
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Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;
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Pornsawan Leaungwutiwong
Pornsawan Leaungwutiwong
Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;
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Charin Thawornkuno
Charin Thawornkuno
Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
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Yupaporn Wattanagoon
Yupaporn Wattanagoon
Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;
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Acute undifferentiated febrile illness (AUFI) has been a diagnostic dilemma in the tropics. Without accurate point-of-care tests, information on local pathogens and clinical parameters is essential for presumptive diagnosis. A prospective hospital-based study was conducted at the Bangkok Hospital for Tropical Diseases from 2013 to 2015 to determine common etiologies of AUFI. A total of 397 adult AUFI cases, excluding malaria by blood smear, were enrolled. Rapid diagnostic tests for tropical infections were performed on admission, and acute and convalescent samples were tested to confirm the diagnosis. Etiologies could be identified in 271 (68.3%) cases. Dengue was the most common cause, with 157 cases (39.6%), followed by murine typhus (20 cases; 5.0%), leptospirosis (16 cases; 4.0%), influenza (14 cases; 3.5%), and bacteremia (six cases; 1.5%). Concurrent infection by at least two pathogens was reported in 37 cases (9.3%). Furthermore, characteristics of dengue and bacterial infections (including leptospirosis and rickettsioses) were compared to facilitate dengue triage, initiate early antibiotic treatment, and minimize unnecessary use of antibiotics. In conclusion, dengue was the most common pathogen for AUFI in urban Thailand. However, murine typhus and leptospirosis were not uncommon. Empirical antibiotic treatment using doxycycline or azithromycin might be more appropriate, but cost–benefit studies are required. Physicians should recognize common causes of AUFI in their localities and use clinical and laboratory clues for provisional diagnosis to provide appropriate treatment while awaiting laboratory confirmation.
Author Notes
Financial support: This study was supported by research fund from the Faculty of Tropical Medicine, Mahidol University, Fiscal Year 2012, Dean’s Research Fund 2012, and ICTM grant from the Faculty of Tropical Medicine, Mahidol University. The publication was also granted by the Faculty of Tropical Medicine, Mahidol University.
Disclaimer: Parts of this work were presented as a poster presentation in Joint International Tropical Medicine Meeting (JITMM) 2015, Bangkok, Thailand, and the 2nd International Meeting on Arboviruses and Their Vectors (IMAV) 2017, Glasgow, United Kingdom.
Authors’ addresses: Viravarn Luvira, Udomsak Silachamroon, Watcharapong Piyaphanee, and Yupaporn Wattanagoon, Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, E-mails: viravarn.luv@mahidol.ac.th, udomsak.sil@mahidol.ac.th, watcharapong.piy@mahidol.ac.th, and yupaporn.wat@mahidol.ac.th. Saranath Lawpoolsri, Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, E-mail: saranath.law@mahidol.ac.th. Wirongrong Chierakul, Department of Clinical Tropical Medicine and Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, E-mail: wirongrong.chi@mahidol.ac.th. Pornsawan Leaungwutiwong, Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, E-mail: pornsawan.lea@mahidol.ac.th. Charin Thawornkuno, Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, E-mail: charin.tha@mahidol.ac.th.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Prasad N, Murdoch DR, Reyburn H, Crump JA, 2015. Etiology of severe febrile illness in low- and middle-income countries: a systematic review. PLoS One 10: e0127962.
-
2.
Crump JA, Kirk MD, 2015. Estimating the burden of febrile illnesses. PLoS Negl Trop Dis 9: e0004040.
-
3.
Suaya JA et al. 2009. Cost of dengue cases in eight countries in the Americas and Asia: a prospective study. Am J Trop Med Hyg 80: 846–855.
-
4.
Tomashek KM et al. 2017. Clinical and epidemiologic characteristics of dengue and other etiologic agents among patients with acute febrile illness, Puerto Rico, 2012–2015. PLoS Negl Trop Dis 11: e0005859.
-
5.
Pappas G, Papadimitriou P, Siozopoulou V, Christou L, Akritidis N, 2008. The globalization of leptospirosis: worldwide incidence trends. Int J Infect Dis 12: 351–357.
-
6.
Chierakul W, 2014. Leptospirosis. Farrar J, Junghanss J, Lalloo D, Hotez PJ, Kang G, White NJ, eds. Manson’s Tropical Diseases. 23rd ed. China: Elsevier, 433–440.
-
7.
Suputtamongkol Y, Suttinont C, Niwatayakul K, Hoontrakul S, Limpaiboon R, Chierakul W, Losuwanaluk K, Saisongkork W, 2009. Epidemiology and clinical aspects of rickettsioses in Thailand. Ann N Y Acad Sci 1166: 172–179.
-
8.
McGready R et al. 2010. Arthropod borne disease: the leading cause of fever in pregnancy on the Thai-Burmese border. PLoS Negl Trop Dis 4: e888.
-
9.
Hamaguchi S et al. 2015. Clinical and epidemiological characteristics of scrub typhus and murine typhus among hospitalized patients with acute undifferentiated fever in northern Vietnam. Am J Trop Med Hyg 92: 972–978.
-
10.
Manock SR et al. 2009. Etiology of acute undifferentiated febrile illness in the Amazon basin of Ecuador. Am J Trop Med Hyg 81: 146–151.
-
11.
Naing C, Kassim AI, 2012. Scaling-up attention to nonmalaria acute undifferentiated fever. Trans R Soc Trop Med Hyg 106: 331–332.
-
12.
Phuong HL, de Vries PJ, Nagelkerke N, Giao PT, Hung le Q, Binh TQ, Nga TT, Nam NV, Kager PA, 2006. Acute undifferentiated fever in Binh Thuan province, Vietnam: imprecise clinical diagnosis and irrational pharmaco-therapy. Trop Med Int Health 11: 869–879.
-
13.
Thipmontree W, Suputtamongkol Y, Tantibhedhyangkul W, Suttinont C, Wongswat E, Silpasakorn S, 2014. Human leptospirosis trends: northeast Thailand, 2001–2012. Int J Environ Res Public Health 11: 8542–8551.
-
14.
Leelarasamee A, Chupaprawan C, Chenchittikul M, Udompanthurat S, 2004. Etiologies of acute undifferentiated febrile illness in Thailand. J Med Assoc Thai 87: 464–472.
-
15.
Suttinont C et al. 2006. Causes of acute, undifferentiated, febrile illness in rural Thailand: results of a prospective observational study. Ann Trop Med Parasitol 100: 363–370.
-
16.
Ellis RD et al. 2006. Causes of fever in adults on the Thai-Myanmar border. Am J Trop Med Hyg 74: 108–113.
-
17.
World Health Organization, 1997. Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control. Available at: http://apps.who.int/iris/bitstream/handle/10665/41988/9241545003_eng.pdf. Accessed June 17, 2018.
-
18.
Kotepui M, PhunPhuech B, Phiwklam N, Uthaisar K, Thirarattanasunthon P, 2017. Prevalence of scrub typhus infection among patients infected with malaria in Phop Phra Hospital, Tak province, Thailand. J Med Tech Assoc Thailand 45: 5909–5916.
-
19.
Chansamouth V et al. 2016. The aetiologies and impact of fever in pregnant inpatients in Vientiane, Laos. PLoS Negl Trop Dis 10: e0004577.
-
20.
Brownlow T, Kavanagh OV, Logan EF, Hartskeerl RA, Savage R, Palmer MF, Krahl M, Mackie DP, Ellis WA, 2014. ‘Leptorapide’–a one-step assay for rapid diagnosis of human leptospirosis. Epidemiol Infect 142: 1182–1187.
-
21.
Surase PV, Nataraj G, Pattamadai K, Mehta PR, Pazare AR, Agarwal MC, Nanavati RN, 2016. An appropriately performed conventional blood culture can facilitate choice of therapy in resource-constrained settings-comparison with BACTEC 9050. J Postgrad Med 62: 228–234.
-
22.
Isenberg HI, 1998. Essential Procedures for Clinical Microbiology. Washington, DC: ASM Press.
-
23.
Johnson BW, Russell BJ, Lanciotti RS, 2005. Serotype-specific detection of dengue viruses in a fourplex real-time reverse transcriptase PCR assay. J Clin Microbiol 43: 4977–4983.
-
24.
Nga TT, Thai KT, Phuong HL, Giao PT, Hung le Q, Binh TQ, Mai VT, Van Nam N, de Vries PJ, 2007. Evaluation of two rapid immunochromatographic assays for diagnosis of dengue among Vietnamese febrile patients. Clin Vaccine Immunol 14: 799–801.
-
25.
World Health Organization, 2009. Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control. Available at: http://www.who.int/tdr/publications/documents/dengue-diagnosis.pdf. Accessed April 12, 2018.
-
26.
Innis BL, Nisalak A, Nimmannitya S, Kusalerdchariya S, Chongswasdi V, Suntayakorn S, Puttisri P, Hoke CH, 1989. An enzyme-linked immunosorbent assay to characterize dengue infections where dengue and Japanese encephalitis co-circulate. Am J Trop Med Hyg 40: 418–427.
-
27.
Stenos J, Graves SR, Unsworth NB, 2005. A highly sensitive and specific real-time PCR assay for the detection of spotted fever and typhus group Rickettsiae. Am J Trop Med Hyg 73: 1083–1085.
-
28.
Sonthayanon P, Chierakul W, Wuthiekanun V, Phimda K, Pukrittayakamee S, Day NP, Peacock SJ, 2009. Association of high Orientia tsutsugamushi DNA loads with disease of greater severity in adults with scrub typhus. J Clin Microbiol 47: 430–434.
-
29.
Smythe LD, Smith IL, Smith GA, Dohnt MF, Symonds ML, Barnett LJ, McKay DB, 2002. A quantitative PCR (TaqMan) assay for pathogenic Leptospira spp. BMC Infect Dis 2: 13.
-
30.
Sittiwangkul R, Pongprot Y, Silviliarat S, Oberdorfer P, Jittamala P, Sirisanthana V, 2008. Acute fulminant myocarditis in scrub typhus. Ann Trop Paediatr 28: 149–154.
-
31.
Crump JA et al. 2013. Etiology of severe non-malaria febrile illness in northern Tanzania: a prospective cohort study. PLoS Negl Trop Dis 7: e2324.
-
32.
Reller ME, Chikeka I, Miles JJ, Dumler JS, Woods CW, Mayorga O, Matute AJ, 2016. First identification and description of rickettsioses and Q fever as causes of acute febrile illness in Nicaragua. PLoS Negl Trop Dis 10: e0005185.
-
33.
Chimsumang S, Chettanadee S, Jitrathai S, Wongchotigul V, 2005. Indirect immunoperoxidase test for the diagnosis of leptospirosis. Southeast Asian J Trop Med Public Health 36: 296–301.
-
34.
World Health Organization, 2013. Laboratory Procedures: Serological Detection of Avian Influenza A(H7N9) Infections by Microneutralization Assay. Available at: http://www.who.int/influenza/gisrs_laboratory/cnic_serological_diagnosis_microneutralization_a_h7n9.pdf. Accessed September 11, 2018.
-
35.
Parker TM, Murray CK, Richards AL, Samir A, Ismail T, Fadeel MA, Jiang J, Wasfy MO, Pimentel G, 2007. Concurrent infections in acute febrile illness patients in Egypt. Am J Trop Med Hyg 77: 390–392.
-
36.
Bharaj P, Chahar HS, Pandey A, Diddi K, Dar L, Guleria R, Kabra SK, Broor S, 2008. Concurrent infections by all four dengue virus serotypes during an outbreak of dengue in 2006 in Delhi, India. Virol J 5: 1.
-
37.
Dhanoa A, Hassan SS, Ngim CF, Lau CF, Chan TS, Adnan NA, Eng WW, Gan HM, Rajasekaram G, 2016. Impact of dengue virus (DENV) co-infection on clinical manifestations, disease severity and laboratory parameters. BMC Infect Dis 16: 406.
-
38.
Suputtamongkol Y et al. 2010. Strategies for diagnosis and treatment of suspected leptospirosis: a cost-benefit analysis. PLoS Negl Trop Dis 4: e610.
-
39.
Phimda K et al. 2007. Doxycycline versus azithromycin for treatment of leptospirosis and scrub typhus. Antimicrob Agents Chemother 51: 3259–3263.
-
40.
Libraty DH et al. 2007. A comparative study of leptospirosis and dengue in Thai children. PLoS Negl Trop Dis 1: e111.
-
41.
Pok KY, Lai YL, Sng J, Ng LC, 2010. Evaluation of nonstructural 1 antigen assays for the diagnosis and surveillance of dengue in Singapore. Vector Borne Zoonotic Dis 10: 1009–1016.
-
42.
Pal S, Dauner AL, Mitra I, Forshey BM, Garcia P, Morrison AC, Halsey ES, Kochel TJ, Wu SJ, 2014. Evaluation of dengue NS1 antigen rapid tests and ELISA kits using clinical samples. PLoS One 9: e113411.
-
43.
Potts JA, Rothman AL, 2008. Clinical and laboratory features that distinguish dengue from other febrile illnesses in endemic populations. Trop Med Int Health 13: 1328–1340.
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