Causes of acute undifferentiated fever and the utility of biomarkers in Chiangrai, northern Thailand.

Tri Wangrangsimakul,Vanaporn Wuthiekanun,Pacharee Kantipong,Achara Laongnualpanich,Stuart D Blacksell,Mavuto Mukaka,Wirongrong Chierakul,Thomas Althaus,Nicholas P Day,Daniel H Paris,Florian Marks

doi:10.1371/journal.pntd.0006477

Tri Wangrangsimakul, Vanaporn Wuthiekanun + Show 9 more

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https://doi.org/10.1371/journal.pntd.0006477

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Abstract

BackgroundTropical 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 findingsA 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.InterpretationScrub 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.

Highlights

Acute undifferentiated fever (AUF) remains the leading cause of hospitalisation among adults and children in urban and rural regions of Southeast Asia
Our results suggest that simple laboratory tests such as full blood count and C-reactive protein (CRP) could be beneficial in differentiating between bacterial and viral infections in acutely febrile patients at the hospital level, while a CRP-based POCT test is likely to be costeffective in community settings in rural Southeast Asia
This study has highlighted the importance of scrub typhus and dengue in the aetiology of AUF in Chiangrai province, northern Thailand

Summary

Introduction

Acute undifferentiated fever (AUF) remains the leading cause of hospitalisation among adults and children in urban and rural regions of Southeast Asia. The causes include common diseases such as dengue, scrub typhus, murine typhus, leptospirosis, and enteric fever, which continue to contribute significantly to the febrile disease burden [1,2,3,4]. In Laos, a prospective multicentre study investigating the causes of non-malarial fever revealed dengue, scrub typhus, Japanese encephalitis and leptospirosis as the major aetiologies in hospitalised adults and children once influenza was excluded [6]. In rural Thailand, dengue, scrub typhus, leptospirosis, murine typhus, and influenza have been identified as the most common causes of AUF among adults and children [4, 7]. 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. There has been increasing focus on biomarkers (i.e. Creactive protein (CRP) and procalcitonin) in delineating bacterial from viral infections

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