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Causes of acute undifferentiated fever and the utility of biomarkers in Chiangrai, northern Thailand.
PLoS Negl Trop Dis 2018; 12(5):e0006477PN

Abstract

BACKGROUND

Tropical infectious diseases like dengue, scrub typhus, murine typhus, leptospirosis, and enteric fever continue to contribute substantially to the febrile disease burden throughout Southeast Asia while malaria is declining. Recently, there has been increasing focus on biomarkers (i.e. C-reactive protein (CRP) and procalcitonin) in delineating bacterial from viral infections.

METHODOLOGY/PRINCIPAL FINDINGS

A prospective observational study was performed to investigate the causes of acute undifferentiated fever (AUF) in adults admitted to Chiangrai Prachanukroh hospital, northern Thailand, which included an evaluation of CRP and procalcitonin as diagnostic tools. In total, 200 patients with AUF were recruited. Scrub typhus was the leading bacterial cause of AUF (45/200, 22.5%) followed by leptospirosis (15/200, 7.5%) and murine typhus (7/200, 3.5%), while dengue was the leading viral cause (23/200, 11.5%). Bloodstream infections contributed to 7/200 (3.5%) of the study cohort. There were 9 deaths during this study (4.5%): 3 cases of scrub typhus, 2 with septicaemia (Talaromyces marneffei and Haemophilus influenzae), and 4 of unknown aetiologies. Rickettsioses, leptospirosis and culture-attributed bacterial infections, received a combination of 3rd generation cephalosporin plus a rickettsia-active drug in 53%, 73% and 67% of cases, respectively. Low CRP and white blood count were significant predictors of a viral infection (mainly dengue) while the presence of an eschar and elevated aspartate aminotransferase and alkaline phosphatase were important predictors of scrub typhus.

INTERPRETATION

Scrub typhus and dengue are the leading causes of AUF in Chiangrai, Thailand. Eschar, white blood count and CRP were beneficial in differentiating between bacterial and viral infections in this study. CRP outperformed procalcitonin although cut-offs for positivity require further assessment. The study provides evidence that accurate, pathogen-specific rapid diagnostic tests coupled with biomarker point-of-care tests such as CRP can inform the correct use of antibiotics and improve antimicrobial stewardship in this setting.

Authors+Show Affiliations

Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.Department of Medicine, Chiangrai Prachanukroh Hospital, Chiangrai, Thailand.Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.Department of Medicine, Chiangrai Prachanukroh Hospital, Chiangrai, Thailand.Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom. Department of Medicine, Swiss Tropical and Public Health Institute, Basel, Switzerland. Faculty of Medicine, University of Basel, Basel, Switzerland.

Pub Type(s)

Journal Article
Observational Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29852003

Citation

Wangrangsimakul, Tri, et al. "Causes of Acute Undifferentiated Fever and the Utility of Biomarkers in Chiangrai, Northern Thailand." PLoS Neglected Tropical Diseases, vol. 12, no. 5, 2018, pp. e0006477.
Wangrangsimakul T, Althaus T, Mukaka M, et al. Causes of acute undifferentiated fever and the utility of biomarkers in Chiangrai, northern Thailand. PLoS Negl Trop Dis. 2018;12(5):e0006477.
Wangrangsimakul, T., Althaus, T., Mukaka, M., Kantipong, P., Wuthiekanun, V., Chierakul, W., ... Paris, D. H. (2018). Causes of acute undifferentiated fever and the utility of biomarkers in Chiangrai, northern Thailand. PLoS Neglected Tropical Diseases, 12(5), pp. e0006477. doi:10.1371/journal.pntd.0006477.
Wangrangsimakul T, et al. Causes of Acute Undifferentiated Fever and the Utility of Biomarkers in Chiangrai, Northern Thailand. PLoS Negl Trop Dis. 2018;12(5):e0006477. PubMed PMID: 29852003.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Causes of acute undifferentiated fever and the utility of biomarkers in Chiangrai, northern Thailand. AU - Wangrangsimakul,Tri, AU - Althaus,Thomas, AU - Mukaka,Mavuto, AU - Kantipong,Pacharee, AU - Wuthiekanun,Vanaporn, AU - Chierakul,Wirongrong, AU - Blacksell,Stuart D, AU - Day,Nicholas P, AU - Laongnualpanich,Achara, AU - Paris,Daniel H, Y1 - 2018/05/31/ PY - 2017/09/08/received PY - 2018/04/24/accepted PY - 2018/6/1/entrez PY - 2018/6/1/pubmed PY - 2018/7/17/medline SP - e0006477 EP - e0006477 JF - PLoS neglected tropical diseases JO - PLoS Negl Trop Dis VL - 12 IS - 5 N2 - BACKGROUND: Tropical infectious diseases like dengue, scrub typhus, murine typhus, leptospirosis, and enteric fever continue to contribute substantially to the febrile disease burden throughout Southeast Asia while malaria is declining. Recently, there has been increasing focus on biomarkers (i.e. C-reactive protein (CRP) and procalcitonin) in delineating bacterial from viral infections. METHODOLOGY/PRINCIPAL FINDINGS: A prospective observational study was performed to investigate the causes of acute undifferentiated fever (AUF) in adults admitted to Chiangrai Prachanukroh hospital, northern Thailand, which included an evaluation of CRP and procalcitonin as diagnostic tools. In total, 200 patients with AUF were recruited. Scrub typhus was the leading bacterial cause of AUF (45/200, 22.5%) followed by leptospirosis (15/200, 7.5%) and murine typhus (7/200, 3.5%), while dengue was the leading viral cause (23/200, 11.5%). Bloodstream infections contributed to 7/200 (3.5%) of the study cohort. There were 9 deaths during this study (4.5%): 3 cases of scrub typhus, 2 with septicaemia (Talaromyces marneffei and Haemophilus influenzae), and 4 of unknown aetiologies. Rickettsioses, leptospirosis and culture-attributed bacterial infections, received a combination of 3rd generation cephalosporin plus a rickettsia-active drug in 53%, 73% and 67% of cases, respectively. Low CRP and white blood count were significant predictors of a viral infection (mainly dengue) while the presence of an eschar and elevated aspartate aminotransferase and alkaline phosphatase were important predictors of scrub typhus. INTERPRETATION: Scrub typhus and dengue are the leading causes of AUF in Chiangrai, Thailand. Eschar, white blood count and CRP were beneficial in differentiating between bacterial and viral infections in this study. CRP outperformed procalcitonin although cut-offs for positivity require further assessment. The study provides evidence that accurate, pathogen-specific rapid diagnostic tests coupled with biomarker point-of-care tests such as CRP can inform the correct use of antibiotics and improve antimicrobial stewardship in this setting. SN - 1935-2735 UR - https://www.unboundmedicine.com/medline/citation/29852003/Causes_of_acute_undifferentiated_fever_and_the_utility_of_biomarkers_in_Chiangrai_northern_Thailand_ L2 - http://dx.plos.org/10.1371/journal.pntd.0006477 DB - PRIME DP - Unbound Medicine ER -