Abstract：
BACKGROUND: Acute undifferentiated fever (AUF) is defined as any febrile illness with a duration of ≤14 days without evidence of localized infection. Most outpatient services and a significant inpatient load in India are contributed by AUF. COVID-19 has recently added to the existing list of common etiologies of AUF. While the rapid diagnostic test (RDT) kits, which are widely used for the detection of common etiologies of AUF, are unreliable, the rise of various inflammatory markers may help identify the probable etiology. This not only results in better diagnosis but also prepares the physician for close monitoring and pooling of resources.
OBJECTIVE: To identify the probable etiology of AUF through inflammatory markers.
OBJECTIVE: To understand the clinical and biochemical parameters as possible predictors of adverse outcomes in AUF.
METHODS: This was a prospective observational study carried out in the Department of Medicine in a tertiary care hospital. The total duration of the study was 1 year. A total of 400 AUF patients [both outpatient department (OPD) and inpatient department (IPD)] fulfilling the eligibility criteria were taken up for the study after consent. Various inflammatory markers, namely erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-dimer, ferritin, and procalcitonin levels along with basic blood and biochemical tests were measured in all qualifying patients at their first visit. The level of rise of all the measured inflammatory markers was analyzed for clues toward identifying the etiology. Also, the possible predictors of adverse outcomes, as defined in the study, were analyzed. Outcome variables are described as mean ± standard deviation. All statistical calculations were done using computer programs Microsoft Excel 2007 (Microsoft Corporation, New York, United States of America) and SPSS (Statistical Product and Service Solutions; SPSS Inc., United States of America) version 21.
RESULTS: The common etiologies in our study contributing to AUF were dengue (31.5%), COVID-19 (18.5%), enteric fever (12.7%), scrub typhus (9.0%), and malaria (6.0%). In 76 cases (19%), the fever was undiagnosed. Enteric fever had highly elevated CRP (>30 mg/L) and moderately elevated D-dimer, ferritin, and procalcitonin. Both nonsevere dengue and COVID-19 had highly elevated D-dimer (>750 ng/mL), but in nonsevere dengue, CRP, ferritin, and procalcitonin were only mildly elevated, whereas in COVID-19, CRP and ferritin were moderately elevated with mildly elevated procalcitonin. Scrub typhus had highly elevated CRP and ferritin [more than four times the upper limit of normal (ULN)], but D-dimer and procalcitonin were only mildly elevated. The mean serum procalcitonin level in enteric fever is significantly higher than the other etiologies of AUF. Our study was correctly able to identify 90.8% of nonsevere dengue, 87.8% of typhoid, 83.6% of COVID-19, and 91.4% of scrub typhus patients based on the inflammatory markers level. Obesity, diabetes (both types 1 and 2), hypertension, coronary artery disease (CAD), malignancy, chronic kidney disease (CKD), and chronic lung disease were significantly associated with adverse outcomes. A significant delay in visiting the hospital after the onset of fever was found in all etiologies of AUF, which had adverse outcomes.
CONCLUSIONS: Our study is one of the few studies comparing the rise in the level of various inflammatory markers among the common etiologies of AUF. The novelty of the study is that it aids in identifying the probable etiology of AUF with good confidence through the levels of inflammatory markers. Also, our study highlights the high-risk factors associated with adverse outcomes in AUF.
OBJECTIVE: To identify the probable etiology of AUF through inflammatory markers.
OBJECTIVE: To understand the clinical and biochemical parameters as possible predictors of adverse outcomes in AUF.
METHODS: This was a prospective observational study carried out in the Department of Medicine in a tertiary care hospital. The total duration of the study was 1 year. A total of 400 AUF patients [both outpatient department (OPD) and inpatient department (IPD)] fulfilling the eligibility criteria were taken up for the study after consent. Various inflammatory markers, namely erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-dimer, ferritin, and procalcitonin levels along with basic blood and biochemical tests were measured in all qualifying patients at their first visit. The level of rise of all the measured inflammatory markers was analyzed for clues toward identifying the etiology. Also, the possible predictors of adverse outcomes, as defined in the study, were analyzed. Outcome variables are described as mean ± standard deviation. All statistical calculations were done using computer programs Microsoft Excel 2007 (Microsoft Corporation, New York, United States of America) and SPSS (Statistical Product and Service Solutions; SPSS Inc., United States of America) version 21.
RESULTS: The common etiologies in our study contributing to AUF were dengue (31.5%), COVID-19 (18.5%), enteric fever (12.7%), scrub typhus (9.0%), and malaria (6.0%). In 76 cases (19%), the fever was undiagnosed. Enteric fever had highly elevated CRP (>30 mg/L) and moderately elevated D-dimer, ferritin, and procalcitonin. Both nonsevere dengue and COVID-19 had highly elevated D-dimer (>750 ng/mL), but in nonsevere dengue, CRP, ferritin, and procalcitonin were only mildly elevated, whereas in COVID-19, CRP and ferritin were moderately elevated with mildly elevated procalcitonin. Scrub typhus had highly elevated CRP and ferritin [more than four times the upper limit of normal (ULN)], but D-dimer and procalcitonin were only mildly elevated. The mean serum procalcitonin level in enteric fever is significantly higher than the other etiologies of AUF. Our study was correctly able to identify 90.8% of nonsevere dengue, 87.8% of typhoid, 83.6% of COVID-19, and 91.4% of scrub typhus patients based on the inflammatory markers level. Obesity, diabetes (both types 1 and 2), hypertension, coronary artery disease (CAD), malignancy, chronic kidney disease (CKD), and chronic lung disease were significantly associated with adverse outcomes. A significant delay in visiting the hospital after the onset of fever was found in all etiologies of AUF, which had adverse outcomes.
CONCLUSIONS: Our study is one of the few studies comparing the rise in the level of various inflammatory markers among the common etiologies of AUF. The novelty of the study is that it aids in identifying the probable etiology of AUF with good confidence through the levels of inflammatory markers. Also, our study highlights the high-risk factors associated with adverse outcomes in AUF.
摘要：
背景：急性未分化发热（AUF）定义为任何发热性疾病，持续时间≤14天，没有局部感染的证据。印度的大多数门诊服务和大量住院人数都是由AUF提供的。COVID-19最近被添加到现有的AUF常见病因列表中。而快速诊断测试(RDT)套件,广泛用于检测AUF的常见病因，是不可靠的,各种炎症标志物的升高可能有助于确定可能的病因.这不仅导致更好的诊断，而且还为医生做好了密切监测和资源汇集的准备。
目的：通过炎症标志物确定AUF的可能病因。
目的：了解临床和生化参数作为AUF不良结局的可能预测因子。
方法：这是一项在三级护理医院的医学部进行的前瞻性观察性研究。研究的总持续时间为1年。在同意后，总共400名符合资格标准的AUF患者[门诊部（OPD）和住院部（IPD）]被纳入研究。各种炎症标志物，即红细胞沉降率(ESR)，C反应蛋白(CRP),D-二聚体,铁蛋白,对所有符合条件的患者进行首次访视时的降钙素原水平以及基础血液和生化检查。分析所有测量的炎症标志物的升高水平，以寻找确定病因的线索。此外，不良结果的可能预测因素，根据研究中的定义，进行了分析。结果变量描述为平均值±标准偏差。所有统计计算均使用计算机程序MicrosoftExcel2007（MicrosoftCorporation，纽约,美利坚合众国)和SPSS(统计产品和服务解决方案；SPSSInc.，美利坚合众国)第21版。
结果：我们研究中导致AUF的常见病因是登革热（31.5％），COVID-19（18.5%），肠热(12.7%)，斑疹伤寒(9.0%),和疟疾(6.0%)。在76例（19%）中，发烧没有被诊断出来。肠热患者CRP高度升高（>30mg/L），D-二聚体中度升高，铁蛋白,和降钙素原.非重度登革热和COVID-19的D-二聚体高度升高（>750ng/mL），但是在不严重的登革热中，CRP,铁蛋白,降钙素原只是轻度升高,而在COVID-19中，CRP和铁蛋白中度升高，降钙素原轻度升高。斑疹伤寒的CRP和铁蛋白高度升高[超过正常上限（ULN）的四倍]，但D-二聚体和降钙素原仅轻度升高。肠热中的平均血清降钙素原水平明显高于AUF的其他病因。我们的研究能够正确识别90.8%的非严重登革热，伤寒的87.8％，根据炎症标志物水平，83.6%的COVID-19和91.4%的斑疹伤寒患者。肥胖,糖尿病（1型和2型），高血压,冠状动脉疾病（CAD），恶性肿瘤，慢性肾脏病（CKD），慢性肺病与不良结局显著相关.在AUF的所有病因中都发现了发烧发作后就诊的明显延迟，有不良后果。
结论：我们的研究是比较AUF常见病因中各种炎症标志物水平升高的少数研究之一。该研究的新颖性在于它有助于通过炎症标记物的水平以良好的信心鉴定AUF的可能病因。此外，我们的研究强调了与AUF不良结局相关的高危因素.
目的：通过炎症标志物确定AUF的可能病因。
目的：了解临床和生化参数作为AUF不良结局的可能预测因子。
方法：这是一项在三级护理医院的医学部进行的前瞻性观察性研究。研究的总持续时间为1年。在同意后，总共400名符合资格标准的AUF患者[门诊部（OPD）和住院部（IPD）]被纳入研究。各种炎症标志物，即红细胞沉降率(ESR)，C反应蛋白(CRP),D-二聚体,铁蛋白,对所有符合条件的患者进行首次访视时的降钙素原水平以及基础血液和生化检查。分析所有测量的炎症标志物的升高水平，以寻找确定病因的线索。此外，不良结果的可能预测因素，根据研究中的定义，进行了分析。结果变量描述为平均值±标准偏差。所有统计计算均使用计算机程序MicrosoftExcel2007（MicrosoftCorporation，纽约,美利坚合众国)和SPSS(统计产品和服务解决方案；SPSSInc.，美利坚合众国)第21版。
结果：我们研究中导致AUF的常见病因是登革热（31.5％），COVID-19（18.5%），肠热(12.7%)，斑疹伤寒(9.0%),和疟疾(6.0%)。在76例（19%）中，发烧没有被诊断出来。肠热患者CRP高度升高（>30mg/L），D-二聚体中度升高，铁蛋白,和降钙素原.非重度登革热和COVID-19的D-二聚体高度升高（>750ng/mL），但是在不严重的登革热中，CRP,铁蛋白,降钙素原只是轻度升高,而在COVID-19中，CRP和铁蛋白中度升高，降钙素原轻度升高。斑疹伤寒的CRP和铁蛋白高度升高[超过正常上限（ULN）的四倍]，但D-二聚体和降钙素原仅轻度升高。肠热中的平均血清降钙素原水平明显高于AUF的其他病因。我们的研究能够正确识别90.8%的非严重登革热，伤寒的87.8％，根据炎症标志物水平，83.6%的COVID-19和91.4%的斑疹伤寒患者。肥胖,糖尿病（1型和2型），高血压,冠状动脉疾病（CAD），恶性肿瘤，慢性肾脏病（CKD），慢性肺病与不良结局显著相关.在AUF的所有病因中都发现了发烧发作后就诊的明显延迟，有不良后果。
结论：我们的研究是比较AUF常见病因中各种炎症标志物水平升高的少数研究之一。该研究的新颖性在于它有助于通过炎症标记物的水平以良好的信心鉴定AUF的可能病因。此外，我们的研究强调了与AUF不良结局相关的高危因素.
