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Background: Recurrent FUO (fever of unknown origin) is a rare subtype of FUO for which diagnostic procedures are ill-defined and outcome data are lacking., Methods: We performed a retrospective multicentre study of patients with recurrent FUO between 1995 and 2018. By multivariate analysis, we identified epidemiological, clinical and prognostic variables independently associated with final diagnosis and mortality., Results: Of 170 patients, 74 (44%) had a final diagnosis. Being ≥ 65 years of age (OR = 5.2; p < 0.001), contributory history (OR = 10.4; p < 0.001), and abnormal clinical examination (OR = 4.0; p = 0.015) independently increased the likelihood of reaching a diagnosis, whereas lymph node and/or spleen enlargement decreased it (OR = 0.2; p = 0.004). The overall prognosis was good; 58% of patients recovered (70% of those with a diagnosis). Twelve (7%) patients died; patients without a diagnosis had a fatality rate of 2%. Being ≥ 65 years of age (OR = 41.3; p < 0.001) and presence of skin signs (OR = 9.5; p = 0.005) significantly increased the risk of death., Conclusion: This study extends the known yield of recurrent FUO and highlights the importance of repeated complete clinical examinations to discover potential diagnostic clues during follow-up. Moreover, their overall prognosis is excellent., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: While presumably less common with modern molecular diagnostic and imaging techniques, fever of unknown origin (FUO) remains a challenge in kidney transplant recipients (KTRs). Additionally, the impact of FUO on patient and graft survival is poorly described., Methods: A cohort of adult KTRs between January 1, 1995 and December 31, 2018 was followed at the University of Wisconsin Hospital. Patients transplanted from January 1, 1995 to December 31, 2005 were included in the "early era"; patients transplanted from January 1, 2006 to December 31, 2018 were included in the "modern era". The primary objective was to describe the epidemiology and etiology of FUO diagnoses over time. Secondary outcomes included rejection, graft and patient survival., Results: There were 5590 kidney transplants at our center during the study window. FUO was identified in 323 patients with an overall incidence rate of .8/100 person-years. Considering only the first 3 years after transplant, the incidence of FUO was significantly lower in the modern era than in the early era, with an Incidence Rate Ratio (IRR) per 100 person-years of .48; 95% CI: .35-.63; p < .001. A total of 102 (31.9%) of 323 patients had an etiology determined within 90 days after FUO diagnosis: 100 were infectious, and two were malignancies. In the modern era, FUO remained significantly associated with rejection (HR = 44.1; 95% CI: 16.6-102; p < .001) but not graft failure (HR = 1.21; 95% CI: .68-2.18; p = .52) total graft loss (HR = 1.17; 95% CI: .85-1.62; p = .34), or death (HR = 1.17; 95% CI: .79-1.76; p = .43., Conclusions: FUO is less common in KTRs during the modern era. Our study suggests infection remains the most common etiology. FUO remains associated with significant increases in risk of rejection, warranting further inquiry into the management of immunosuppressive medications in SOT recipients in the setting of FUO., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Accurate and interpretable differential diagnostic technologies are crucial for supporting clinicians in decision-making and treatment-planning for patients with fever of unknown origin (FUO). Existing solutions commonly address the diagnosis of FUO by transforming it into a multi-classification task. However, after the emergence of COVID-19 pandemic, clinicians have recognized the heightened significance of early diagnosis in patients with FUO, particularly for practical needs such as early triage. This has resulted in increased demands for identifying a wider range of etiologies, shorter observation windows, and better model interpretability. In this article, we propose an interpretable hierarchical multimodal neural network framework (iHMNNF) to facilitate early diagnosis of FUO by incorporating medical domain knowledge and leveraging multimodal clinical data. The iHMNNF comprises a top-down hierarchical reasoning framework (Td-HRF) built on the class hierarchy of FUO etiologies, five local attention-based multimodal neural networks (La-MNNs) trained for each parent node of the class hierarchy, and an interpretable module based on layer-wise relevance propagation (LRP) and attention mechanism. Experimental datasets were collected from electronic health records (EHRs) at a large-scale tertiary grade-A hospital in China, comprising 34,051 hospital admissions of 30,794 FUO patients from January 2011 to October 2020. Our proposed La-MNNs achieved area under the receiver operating characteristic curve (AUROC) values ranging from 0.7809 to 0.9035 across all five decomposed tasks, surpassing competing machine learning (ML) and single-modality deep learning (DL) methods while also providing enhanced interpretability. Furthermore, we explored the feasibility of identifying FUO etiologies using only the first N-hour time series data obtained after admission.

Despite an essential differential diagnosis for fever of unknown origin (FUO) in young adults, adult-onset Still's disease (AOSD) is infrequently considered and remained underdiagnosed in low-middle-income countries. The present study analyzed the clinical, serological, radiological, and pathological characteristics of AOSD presented as FUO in India. A hospital-based retrospective study of patients aged > 13 years admitted with FUO and later diagnosed with AOSD in Postgraduate Institute of Medical Education and Research, Chandigarh (India), was conducted between January 2014 and December 2020. Petersdorf and Beeson's criteria were used to define FUO. The diagnosis of AOSD was made based on Yamaguchi's criteria. Twenty-seven patients (median age 26 years, 14 females) were enrolled. All presented with intermittent fever with a median duration of 10 weeks. The typical features of AOSD at admission were arthralgia (n = 24), hepatosplenomegaly (n = 21), spiking fever ≥ 39 °C (n = 19), lymphadenopathy (n = 18), typical rash (n = 17), and sore throat (n = 11). Leukocytosis (n = 25) and neutrophilia (n = 19) were frequent. Hyperferritinemia was universal (range, 700-145,003 ng/ml; ≥ 2000, n = 23). At admission, AOSD was suspected in only nine FUO cases, while tuberculosis (n = 16), undifferentiated connective tissue disorder (n = 14), and lymphoproliferative disorder (n = 11) were common diagnostic possibilities. Crispin et al. clinical scale detected AOSD in only 15 (55.5%) FUO patients. Whole-body imaging (n = 27), including fluorodeoxyglucose positron emission tomography (n = 12), demonstrated reticuloendothelial organ-system involvement and serositis. Seventeen (63%) patients had macrophage activation syndrome at the time of AOSD diagnosis. AOSD FUO presents with typical but nonspecific features; thus, early differentiation from common causes (e.g., tuberculosis, lymphoma) is difficult. Macrophage activation syndrome is common in AOSD with FUO presentation., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: There has been little research on the long-term clinical outcomes of patients discharged due to undiagnosed fevers of unknown origin (FUO). The purpose of this study was to determine how fever of unknown origin (FUO) evolves over time and to determine the prognosis of patients in order to guide clinical diagnosis and treatment decisions., Methods: Based on FUO structured diagnosis scheme, prospectively included 320 patients who hospitalized at the Department of Infectious Diseases of the Second Hospital of Hebei Medical University from March 15, 2016 to December 31,2019 with FUO, to analysis the cause of FUO, pathogenetic distribution and prognosis, and to compare the etiological distribution of FUO between different years, genders, ages, and duration of fever., Results: Among the 320 patients, 279 were finally diagnosed through various types of examination or diagnostic methods, and the diagnosis rate was 87.2%. Among all the causes of FUO, 69.3% were infectious diseases, of which Urinary tract infection 12.8% and lung infection 9.7% were the most common. The majority of pathogens are bacteria. Among contagious diseases, brucellosis is the most common. Non-infectious inflammatory diseases were responsible for 6.3% of cases, of which systemic lupus erythematosus(SLE) 1.9% was the most common; 5% were neoplastic diseases; 5.3% were other diseases; and in 12.8% of cases, the cause was unclear. In 2018-2019, the proportion of infectious diseases in FUO was higher than 2016-2017 (P < 0.05). The proportion of infectious diseases was higher in men and older FUO than in women and young and middle-aged (P < 0.05). According to follow-up, the mortality rate of FUO patients during hospitalization was low at 1.9%., Conclusions: Infectious diseases are the principal cause of FUO. There are temporal differences in the etiological distribution of FUO, and the etiology of FUO is closely related to the prognosis. It is important to identify the etiology of patients with worsening or unrelieved disease., (© 2023. The Author(s).)

Fever of unknown origin (FUO) is a serious challenge for physicians. The aim of the present study was to consider epidemiology and dynamics of FUO in countries with different economic development. The data of FUO patients hospitalized/followed between 1st July 2016 and 1st July 2021 were collected retrospectively and submitted from referral centers in 21 countries through ID-IRI clinical research platform. The countries were categorized into developing (low-income (LI) and lower middle-income (LMI) economies) and developed countries (upper middle-income (UMI) and high-income (HI) economies). This research included 788 patients. FUO diagnoses were as follows: infections (51.6%; n = 407), neoplasms (11.4%, n = 90), collagen vascular disorders (9.3%, n = 73), undiagnosed (20.1%, n = 158), miscellaneous diseases (7.7%, n = 60). The most common infections were tuberculosis (n = 45, 5.7%), brucellosis (n = 39, 4.9%), rickettsiosis (n = 23, 2.9%), HIV infection (n = 20, 2.5%), and typhoid fever (n = 13, 1.6%). Cardiovascular infections (n = 56, 7.1%) were the most common infectious syndromes. Only collagen vascular disorders were reported significantly more from developed countries (RR = 2.00, 95% CI: 1.19-3.38). FUO had similar characteristics in LI/LMI and UMI/HI countries including the portion of undiagnosed cases (OR, 95% CI; 0.87 (0.65-1.15)), death attributed to FUO (RR = 0.87, 95% CI: 0.65-1.15, p-value = 0.3355), and the mean duration until diagnosis (p = 0.9663). Various aspects of FUO cannot be determined by the economic development solely. Other development indices can be considered in future analyses. Physicians in different countries should be equally prepared for FUO patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Human brucellosis has become one of the major public health problems in China, and increases atypical manifestations, such as fever of unknown origin (FUO), and misdiagnosis rates has complicated the diagnosis of brucellosis. To date, no relevant study on the relationship between brucellosis and FUO has been conducted., Methods: We retrospectively reviewed the medical charts of 35 patients with confirmed human brucellosis and prospectively recorded their outcomes by telephone interview. The patients were admitted to the Second Affiliated Hospital of Nanchang University between January 01, 2013 and October 31, 2019. Patient data were collected from hospital medical records., Results: The percentage of males was significantly higher than that of female in FUO (78.95% vs. 21.05%, P < 0.05), and 80% of the patients had a clear history of exposure to cattle and sheep. Moreover, 19 (54%) cases were hospitalized with FUO, among which the patients with epidemiological histories were significantly more than those without (P < 0.05). The incidence of toxic hepatitis in FUO patients was higher than that in non-FUO patients (89% vs. 50%, P < 0.05). Meanwhile, the misdiagnosis rate was considerably higher in the FUO group than in the non-FUO group (100% vs. 63%; P < 0.05)., Conclusion: Brucellosis is predominantly FUO admission in a non-endemic area of China, accompanied by irregular fever and toxic hepatitis. Careful examination of the epidemiological history and timely improvement of blood and bone marrow cultures can facilitate early diagnosis and prevent misdiagnosis., (© 2022. The Author(s).)

Pyrexia of unknown origin (PUO) and its aetiology vary considerably according to geography. We conducted a retrospective study to update our knowledge of PUO in Pakistan. PUO was defined as a febrile illness of >3 weeks' duration, a temperature of >38.3°C, and >3 outpatient visits or 3 days' hospitalization. Infection was the cause in 47.1%, malignancy in 23.1%, noninfectious inflammatory disease in 21.8%, miscellaneous causes in 1.2%, and in 6.8%, the cause of the fever was not found.

Background: Diagnostic tools for determining causes of fever of unknown origin (FUO) have improved over time. We examined if cancer incidence among these patients changed over a 20-year period., Methods: Population-based cohort study using nationwide Danish registries. We identified individuals diagnosed with FUO (1998-2017) to quantify their excess risk of cancer compared with the general population. Follow-up for cancer started 1 month after FUO. We computed absolute risks and standardized incidence ratios (SIRs) of cancer, and mortality rate ratios adjusted for age, sex, and cancer stage., Results: Among 6620 patients with FUO (46.9% male; median age: 39 years), 343 were diagnosed with cancer (median follow-up: 6.5 years). The 1- to <12-month risk was 1.2%, and the SIR was 2.3 (95% CI, 1.8-2.9). The increased 1- to <12-month SIR was mainly due to an excess of Hodgkin lymphoma (SIR = 41.7) non-Hodgkin lymphoma (SIR = 16.1), myelodysplastic syndrome/chronic myeloproliferative diseases (SIR = 6.0), lower gastrointestinal cancer (SIR = 3.3), and urinary tract cancer (SIR = 2.9). Beyond 1-year follow-up, malignant melanoma, hepatobiliary tract/pancreatic cancer, and brain/CNS/eye cancer were diagnosed more often than expected. The 1- to <12-month cancer SIR attenuated over time, and for the 2013-2017 period we found no excess risk. Patients diagnosed with cancer ≤1 year after FUO had similar mortality to cancer patients without this diagnosis., Conclusions: Patients with FUO have a higher 1- <12-month cancer SIR; thereafter, the incidence for most cancers equals that of the general population. Decreasing SIRs over time suggests improvements in the initial diagnostic workup for FUO., Competing Interests: Potential conflicts of interest. H. T. S. does not report receiving fees, honoraria, grants, or consultancies. However, the Department of Clinical Epidemiology is involved in studies with funding from various companies as research grants to (and administered by) Aarhus University. None of these grants are related to the current study. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Importance: Patients meeting the criteria for fever of unknown origin (FUO) can be evaluated with structured or nonstructured approaches, but the optimal diagnostic method is unresolved., Objective: To analyze differences in diagnostic outcomes among patients undergoing structured or nonstructured diagnostic methods applied to prospective clinical studies., Data Sources: PubMed, Embase, Scopus, and Web of Science databases with librarian-generated query strings for FUO, PUO, fever or pyrexia of unknown origin, clinical trial, and prospective studies identified from January 1, 1997, to March 31, 2021., Study Selection: Prospective studies meeting any adult FUO definition were included. Articles were excluded if patients did not precisely fit any existing adult FUO definition or studies were not classified as prospective., Data Extraction and Synthesis: Abstracted data included years of publication and study period, country, setting (eg, university vs community hospital), defining criteria and category outcome, structured or nonstructured diagnostic protocol evaluation, sex, temperature threshold and measurement, duration of fever and hospitalization before final diagnoses, and contribution of potential diagnostic clues, biochemical and immunological serologic studies, microbiology cultures, histologic analysis, and imaging studies. Structured protocols compared with nonstructured diagnostic methods were analyzed using regression models., Main Outcomes and Measures: Overall diagnostic yield was the primary outcome., Results: Among the 19 prospective trials with 2627 unique patients included in the analysis (range of patient ages, 10-94 years; 21.0%-55.3% female), diagnoses among FUO series varied across and within World Health Organization (WHO) geographic regions. Use of a structured diagnostic protocol was not significantly associated with higher odds of yielding a diagnosis compared with nonstructured protocols in aggregate (odds ratio [OR], 0.98; 95% CI, 0.65-1.49) or between Western Europe (Belgium, France, the Netherlands, and Spain) (OR, 0.95; 95% CI, 0.49-1.86) and Eastern Europe (Turkey and Romania) (OR, 0.83; 95% CI, 0.41-1.69). Despite the limited number of studies in some regions, analyses based on the 6 WHO geographic areas found differences in the diagnostic yield. Western European studies had the lowest percentage of achieving a diagnosis. Southeast Asia led with infections at 49.0%. Noninfectious inflammatory conditions were most prevalent in the Western Pacific region (34.0%), whereas the Eastern Mediterranean region had the highest proportion of oncologic explanations (24.0%)., Conclusions and Relevance: In this systematic review and meta-analysis, diagnostic yield varied among WHO regions. Available evidence from prospective studies did not support that structured diagnostic protocols had a significantly better rate of achieving a diagnosis than nonstructured protocols. Clinicians worldwide should incorporate geographical disease prevalence in their evaluation of patients with FUO.

Objective: To date, there is no standard diagnostic practice to identify the underlying disease-causing mechanism for paediatric patients suffering from chronic fever without any specific diagnosis, which is one of the leading causes of death in paediatric patients. Therefore, we aimed this retrospective study to analyse medical records of paediatric patients with fever of unknown origin (FUO) to provide a preliminary basis for improving the diagnostic categories and facilitate the treatment outcomes., Design: A retrospective study., Setting: Beijing Children's Hospital., Participants: Clinical data were collected from 1288 children between 1 month and 18 years of age diagnosed with FUO at Beijing Children's Hospital between January 2010 and December 2017., Interventions: According to the aetiological composition, age, duration of fever and laboratory examination results, the diagnostic strategies were analysed and formulated., Primary and Secondary Outcome Measures: The statistical analyses were carried out using SPSS V.24.0 platform along with the χ 2 test and analysis of variance (p<0.05)., Results: The duration of fever ranged from 2 weeks to 2 years, with an average of 6 weeks. There were 656 cases (50.9%) of infectious diseases, 63 cases (4.9%) of non-infectious inflammatory diseases (NIIDs), 86 cases (6.7%) of neoplastic diseases, 343 cases (26.6%) caused by miscellaneous diseases and 140 cases (10.9%) were undiagnosed. With increasing age, the proportion of FUO from infectious diseases gradually decreased from 73.53% to 44.21%. NIID was more common in children over 3 years old, and neoplastic diseases mainly occurred from 1 to 6 years of age. Among miscellaneous diseases, the age distribution was mainly in school-aged children over 6 years. Respiratory tract infection was the most common cause of FUO in children, followed by bloodstream infections. Bacterial infection was the most common cause in children with less than 1 year old, while the virus was the main pathogen in children over 1 year old., Conclusions: The diagnosis of neoplastic diseases and miscellaneous diseases-related diseases still depends mainly on invasive examination. According to our clinical experience, the diagnostic process was formulated based on fever duration and the type of disease. This process can provide a guide for the diagnosis and treatment of paediatric FUO in the future., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Fever of unknown origin (FUO) is a challenge for clinicians treating patients with HIV/AIDS. CD4 counts can be helpful in the diagnosis and treatment. This study aimed to determine several common etiologies of FUO stratified by CD4 count levels in HIV/AIDS patients., Methods: A cross-sectional retrospective and prospective study was conducted in 195 HIV/AIDS patients with FUO admitted to the National Hospital for Tropical Diseases from January 2016 to June 2019. Clinical parameters, immune status, and etiologies for each patient were recorded. Odds ratios were calculated to compare the distributions of common etiologies in groups with two different CD4 count levels: < 50 cells/mm 3 and ≥ 50 cells/mm 3 ., Results: The proportions of opportunistic infections and noninfectious etiologies were 93.3% and 3.6%, respectively. Tuberculosis was the most common opportunistic infection (46.7%), followed by talaromycosis (29.2%) and Pneumocystis jiroveci (PCP) infection (20.5%). Tuberculosis was predominant in all CD4 level groups. Most patients with talaromycosis had CD4 counts below 50 cells/mm 3 . In total, 53.8% of the patients were infected by one pathogen. The risks of tuberculosis and talaromycosis in FUO-HIV patients were high when their CD4 counts were below 50 cells/mm 3 ., Conclusions: Opportunistic infections, especially tuberculosis, are still the leading cause of FUO in HIV/AIDS patients. Tuberculosis and Talaromyces marneffei (TM) infection should be considered in patients with CD4 cell counts < 50 cells/mm 3 . This study implies that guidelines for appropriate testing to identify the etiology of FUO in HIV/AIDS patient based on the CD4 cell count should be developed, thereby reducing resource waste., (© 2022. The Author(s).)

Patients treated for adult T-Cell leukemia/lymphoma (ATL) have a poor prognosis and are prone to infectious complications which are poorly described. As the French reference center for ATL, we retrospectively analyzed 47 consecutive ATL (acute, n = 23; lymphoma, n = 14; chronic, n = 8; smoldering, n = 2) patients between 2006 and 2016 (median age 51 years, 96% Afro-Caribbean origin). The 3-year overall survival (OS) was 15.8%, 11.3%, and 85.7% for acute, lymphoma, and indolent (chronic and smoldering) forms respectively. Among aggressive subtypes, 20 patients received, as frontline therapy, high dose of zidovudine and interferon alfa (AZT-IFN⍺) resulting in an overall response rate (ORR) of 39% (complete response [CR] 33%) and 17 chemotherapy resulting of an ORR of 59% (CR 50%). Ninety-five infections occurred in 38 patients, most of whom had an acute subtype (n = 73/95; 77%). During their follow-up, patients receiving frontline chemotherapy or frontline AZT-IFNα developed infections in 74% (n = 14/19) and 89% (n = 24/27) of the cases respectively. Sixty-four (67%) of infections were microbiologically documented. Among them, invasive fungal infections (IFI, n = 11) included 2 Pneumocystis jirovecii pneumonia, 5 invasive aspergillosis, and 4 yeast fungemia. IFI exclusively occurred in patients with acute subtype mostly exposed to AZT-IFNα (n = 10/11) and experiencing prolonged (> 10 days) grade 4 neutropenia. Patients with aggressive subtype experiencing IFI had a lower OS than those who did not (median OS 5.4 months versus 18.4 months, p = 0.0048). ATL patients have a poor prognosis even in the modern era. Moreover, the high rate of infections impacts their management especially those exposed to AZT-IFNα., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Fever of unknown origin (FUO) has different etiology in different age groups. We aimed to determine the spectrum of FUO in older patients and to establish the underlying etiology., Methods: This was a hospital-based prospective observational study conducted between January 2018 to June 2019 at Postgraduate Institute of Medical Education and Research, Chandigarh, India. Fifty-one consecutive patients aged 60 years and above met the qualitative criteria of FUO., Results: The etiological distribution was infections in 21 patients (41.2%), malignancies in 16 (31.4%) and noninfectious inflammatory disorders in 8 (15.7%). Six patients (11.8%) remained undiagnosed. Among infections, 15 patients (29.4%) had tuberculosis, and 10 had an extrapulmonary disease. Twelve out of 16 cases with malignancies had a hematological cause, and eight had lymphoma. ;Regarding decisive methods of diagnosis, 18F-fluorodeoxyglucose positron emission tomography was diagnostic in 17 out of 27 patients (63%) and computed tomography in 21 out of 42 cases (50%). Imaging or endoscopy-guided procedures provided a diagnostic clue in 12 out of 14 patients (85.7%), and bone marrow examination results were useful in 9 out of 19 (47.4%)., Conclusions: Infections and malignancies contributed to about three-fourths of cases, with tuberculosis and lymphoma being the commonest etiologies., (© Journal of the Association of Physicians of India 2011.)

Aims: The differential diagnosis of Fever of Unknown Origin (FUO) is still a major clinical challenge despite the advances in diagnostic procedures. In this multicentre study, we aimed to reveal FUO aetiology and factors influencing the final diagnosis of FUO in Turkey., Methods: A total of 214 patients with FUO between the years 2015 and 2019 from 13 tertiary training and research hospitals were retrospectively evaluated., Results: The etiologic distribution of FUO was infections (44.9%), malignancies (15.42%), autoimmune/inflammatory (11.68%) diseases, miscellaneous diseases (8.41%) and undiagnosed cases (19.62%). Brucellosis (10.25%), extrapulmonary tuberculosis (6.54%) and infective endocarditis (6.54%) were the most frequent three infective causes. Solid malignancies (7.1%) and lymphoma (5.6%), adult-onset still's disease (6.07%) and thyroiditis (5.14%) were other frequent diseases. The aetiological spectrum did not differ in elderly people (P < .05). Infections were less frequent in Western (34.62%) compared with Eastern regions of Turkey (60.71%) (P < .001, OR: 0.31, 95% Cl: 0.19 to 0.60). The ratio of undiagnosed aetiology was significantly higher in elderly people (p: 0.046, OR: 2.34, 95% Cl: 1.00 to 5.48) and significantly lower in Western Turkey (P: .004, OR: 3.07, 95% Cl: 1.39 to 6.71)., Conclusions: Brucellosis, extrapulmonary tuberculosis and infective endocarditis remain to be the most frequent infective causes of FUO in Turkey. Solid tumours and lymphomas, AOSD and thyroiditis are the other common diseases. The aetiological spectrum did not differ in elderly people, on the other hand, infections were more common in Eastern Turkey. A considerable amount of aetiology remained undiagnosed despite the state-of-the-art technology in healthcare services., (© 2021 John Wiley & Sons Ltd.)

Background: The rampant spread of the novel coronavirus disease (COVID-19) has assumed pandemic proportions across the world. Attempts to contain its spread have entailed varying early screening and triage strategies implemented in different countries and regions., Aim: To share the experience of scientific and standardized management of fever clinics in China, which provide the first effective checkpoint for the prevention and control of COVID-19., Introduction: A fever clinic was established at our hospital in Tianjin, China, for initially identifying suspected cases of COVID-19 and controlling the spread of the disease., Methods: The management system covered the following aspects: spatial layout; partitioning of functional zones; a work management system and associated processes; management of personnel, materials and equipment; and patient education., Results: Within two months of introducing these measures, there was a comprehensive reduction in the number of new COVID-19 cases in Tianjin, and zero infections occurred among medical staff at the fever clinic., Discussion: The fever clinic plays an important role in the early detection, isolation and referral of patients presenting with fevers of unknown origin. Broad screening criteria, an adequate warning mechanism, manpower reserves and staff training at the clinic are essential for the early management of epidemics., Conclusion: The spread of COVID-19 has been effectively curbed through the establishment of the fever clinic, which merits widespread promotion and application., Implications for Nursing and Health Policies: Health managers should be made aware of the important role of fever clinics in the early detection, isolation and referral of patients, and in the treatment of infectious diseases to prevent and control their spread. In the early stage of an epidemic, fever clinics should be established in key areas with concentrated clusters of cases. Simultaneously, the health and safety of health professionals require attention., (© 2021 International Council of Nurses.)

Introduction: Acute fever of unknown origin (FUO) in children under 29 days is a worrying situation because of the risk of serious bacterial infection (SBI)., Objective: to study the main clinical and laboratory characteristics of a group of hospitalized children under 29 days with diagnosis of FUO., Patients and Method: Retrospective study of children under 29 days hospitalized due to FUO. The clinical records of the patients were reviewed, recording age, sex, history of fever before consultation, temperature at admission, estimated severity at admission and discharge, discharge diagnoses, laboratory tests, and indicated treatments. Patients were classified according to the severity of the discharge diagnosis, as severe (S) and non-severe (NS). The inclusion criteria were term newborn, age less than 29 days, fe ver > 38°C registered at home or admission, and history of < 4 days., Results: 468 children with FUO were admitted. Concordance between severity at admission and discharge was low (Kappa = 0.125; p = 0.0007). 26.1% of children were S and 73.9% NS. In the S group, urinary tract infection domínate (70.5%) and in the NS, FUO (67.6%). The cut-off levels for leukocytes/mm3, C-reactive protein, and neutrophils/mm3 showed negative predictive values to rule out severe bacterial infection. Conclu sions: Most of the newborns presented mild severity at admission, but 24% of them had SBI, thus hospitalization and close clinical observation are always necessary. Laboratory tests, such as CRP, white blood cell and neutrophils count are not good predictors of SBI. Early treatment with antibio tics for patients who meet the low-risk criteria is debatable.

Background: Our purpose was to provide a detailed clinical description, of symptoms and laboratory abnormalities, and temporality in patients with confirmed Zika and dengue infections, and other acute illnesses of unidentified origin (AIUO)., Methods/ Principal Findings: This was a two-year, multicenter, observational, prospective, cohort study. We collected data from patients meeting the Pan American Health Organization's modified case-definition criteria for probable Zika infection. We identified Zika, dengue chikungunya by RT-PCR in serum and urine. We compared characteristics between patients with confirmed Zika and dengue infections, Zika and AIUO, and Dengue and AIUO at baseline, Days 3,7,28 and 180 of follow-up. Most episodes (67%) consistent with the PAHO definition of probable Zika could not be confirmed as due to any flavivirus and classified as Acute Illnesses of Unidentified Origin (AIUO). Infections by Zika and dengue accounted for 8.4% and 16% of episodes. Dengue patients presented with fever, generalized non-macular rash, arthralgia, and petechiae more frequently than patients with Zika during the first 10 days of symptoms. Dengue patients presented with more laboratory abnormalities (lower neutrophils, lymphocytosis, thrombocytopenia and abnormal liver function tests), with thrombocytopenia lasting for 28 days. Zika patients had conjunctivitis, photophobia and localized macular rash more frequently than others. Few differences persisted longer than 10 days after symptoms initiation: conjunctivitis in Zika infections, and self-reported rash and petechia in dengue infections., Conclusions: Our study helps characterize the variety and duration of clinical features in patients with Zika, dengue and AIUO. The lack of diagnosis in most patients points to need for better diagnostics to assist clinicians in making specific etiologic diagnoses., Competing Interests: The authors have declared that no competing interests exist.

The aetiology of pyrexia of unknown origin (PUO) varies dramatically according to epidemiology. We studied the cause and spectrum of PUO in Indian adults. A total of 152 patients (112 prospectively and 40 retrospectively) met Petersdorf and Beeson's criteria. The diagnostic evaluation was guided by potentially diagnostic clues, based on a 'step-wise' approach. The five main categories, i.e. infectious, neoplastic, non-infectious inflammatory, miscellaneous and undiagnosed comprised 43.4%, 21.5%, 19.7%, 2.0% and 12.5%, respectively. The top three causes were tuberculosis (n = 43, 28.3%), lymphoma (n = 19, 12.5%) and adult-onset Still's disease (n = 12, 7.9%). Tuberculosis predominated in all age groups, and about 70% of cases had the extrapulmonary form, the most common being gastrointestinal. Hodgkin and non-Hodgkin lymphomas were equally distributed, but solid malignancies were uncommon. Adult-onset Still's disease was the second commonest cause in adults aged ≤ 40 years. Fever resolved spontaneously in 12/19 cases of undiagnosed cause. Extrapulmonary tuberculosis remains the most prevalent PUO in India.

Background: The Dutch fever without an apparent source (FWS) guidelines were published to timely recognize and treat serious infections. We determined the adherence to the Dutch FWS guidelines and the percentage of serious infections in infants younger than 3 months of age. Second, we identified which clinical criteria, diagnostic tests, and management were associated with nonadherence to the guidelines., Methods: A retrospective cohort study was performed in 2 Dutch teaching hospitals. We assessed the charts of all infants with FWS who presented at the emergency departments from September 30, 2017, to October 1, 2019. Diagnostic and therapeutic decisions were compared with the recommendations, as published in the Dutch guidelines. Infants were categorized into the nonadherence group in case 1 or more recommendations were not adhered to., Results: Data on 231 infants were studied; 51.5% of the cases adhered to the Dutch guidelines and 16.0% suffered from a serious infection. The percentage of infants with a serious infection was higher in the adherence compared with the nonadherence group. We observed no relevant differences in clinical outcomes. Univariate regression analysis showed that an abnormal white blood cell count was associated with nonadherence (OR 0.4, P = 0.049). Not obtaining a urine and blood culture and not starting intravenous antibiotic treatment were the most frequent reasons for nonadherence to the guidelines., Conclusions: Our study indicates that there was nonadherence in a large proportion of FWS cases. The guidelines may need to be adjusted to increase adherence.

Background: Fever of unknown origin (FUO) remains an important public health problem. With malaria transmission declining in some parts of Africa, the evidence suggests other infectious agents now account for most FUO. The purpose of this study was to identify the etiologic agents of FUO in a cross-section of patients at the Mnazi Mmoja hospital in Zanzibar, Tanzania., Methodology: A multiplex TaqMan gene expression Array Card (TAC) and plates were used for detection and classification of different pathogens in blood samples obtained from patients with FUO. Logistic regression analyses was performed using pathogens detected and sociodemographic characteristics as outcome and exposure variables respectively. Odd ratios and 95% confidence interval were calculated and statistical significance was set at P < .05., Result: Thirty-three different pathogens were detected in 27 patient blood samples. The following pathogens were detected in decreasing order of prevalence; Dengue virus, Plasmodium species, Rickettsia, Brucella species, Salmonella typhi, and less than 1% for each of Bartonella, Coxiella burnetii, Salmonella species, and Leptospira. Co-infections of Plasmodium with Dengue and S. typhi were also detected, including one case with three different pathogens-Plasmodium, Rickettsia and Brucella. There was no association between the etiologic agents of FUO and demographic or clinical characteristics., Conclusions: Zoonotic and arboviral etiological agents of fever of unknown origin are present among patients at the Mnazi Mmoja hospital in Zanzibar, Tanzania. There is a need to develop a baseline of standardized diagnostic approaches particularly within the hospital setting. In areas with low malaria prevalence like Zanzibar, Dengue, Rickettsia, Coxiella burnetii, Brucellosis should be considered by clinicians in the differential diagnoses of FUO.

Background: This study aimed to elucidate the etiologies and diagnostic errors of early-phase pediatric fever without an obvious cause., Methods: This single-center, retrospective, descriptive study included 1334 febrile children hospitalized at Beppu Medical Center in Japan between 2014 and 2018. Eligibility criteria were age ≤12 years, axillary temperature ≥38.0°C, and fever duration ≤7 days at admission. Initial diagnoses on the day of admission and final diagnoses at defervescence were divided into initial fever with identified source (FIS) and initial fever without source (FWS) and final FIS and final FWS, respectively. The etiology of initial FWS and diagnostic discordance between initial FIS and final FIS were investigated., Results: Of the 1334 participants, 94 (7.0%) were diagnosed with initial FWS. Among patients with initial FWS, final diagnoses were confirmed in 40 (43%), including Kawasaki disease in 17, urinary tract infection in 5, bacteremia in 4, exanthem subitum in 3, and the others in 11. Among the 1275 patients diagnosed with final FIS, diagnostic discordances between initial and final diagnoses were observed in 131 patients (10%). The multiple logistic regression analysis identified increased serum C-reactive protein value at admission (odds ratio [OR]: 1.09; 95% confidence interval [CI]: 1.06-1.13), exanthem subitum (OR: 409; 95% CI: 119-1399), and Kawasaki disease (OR: 14.3; 95% CI: 8.7-23.3) as independent risk factors for diagnostic discordance., Conclusion: Exanthem subitum and Kawasaki disease may be undiagnosed or misdiagnosed in febrile children with fever duration ≤7 days., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: Patients suffering from haemato-oncological diseases tend to have a weakened immune system after the end of their therapy. To avoid infections, patients are advised to limit contact with other people. This poses the question whether a stay at a rehabilitation facility can be recommended., Methods: We report about 134 rehabilitation stays of patients. Premature discontinuation of the rehabilitation stay was selected as the criterion for a serious complication during the rehabilitation, and the underlying reasons were analysed., Results: Compared to the discontinuation rates of patients suffering from solid tumours (2.4%), the percentage of haemato-oncological patients ending prematurely their rehabilitation stay (8.2%) is significantly increased. This rises to 17.1% for patients who have undergone an allogeneic stem cell transplantation. The analysis of the discontinuation reasons revealed that they were not directly connected to the rehabilitation. Apart from the already known risk factors for premature termination of the rehabilitation stay, we have identified the period (days) between the last therapy and the beginning of the rehabilitation stay as a risk factor., Conclusions: We show for the first time that a rehabilitation stay does not pose additional risks for patients suffering from haemato-oncological diseases., (© 2019 John Wiley & Sons Ltd.)

Background: While health providers consistently use malaria rapid diagnostic tests to rule out malaria, they often lack tools to guide treatment for those febrile patients who test negative. Without the tools to provide an alternative diagnosis, providers may prescribe unnecessary antibiotics or miss a more serious condition, potentially contributing to antibiotic resistance and/or poor patient outcomes., Methods: This study ascertained which diagnoses and treatments might be associated with poor outcomes in adults who test negative for malaria. Adult patients for rapid diagnostic test of malaria seen in mobile health clinics in Mulanje and Phalombe districts were followed for 14 days. Participants were interviewed on sociodemographic characteristics, health-seeking behaviour, diagnosis, treatment and access to care. Mobile clinic medical charts were reviewed. Two weeks (±2 days) following clinic visit, follow-up interviews were conducted to assess whether symptoms had resolved., Results: Initially, 115 adult patients were enrolled and 1 (0.88%) was lost to follow-up. Of the 114 adult patients remaining in the study, 55 (48%) were seen during the dry season and 59 (52%) during the wet season. Symptoms resolved in 90 (80%) patients at the 14-day follow-up visit (n=90) with the rest (n=24) reporting no change in symptoms. None of the patients in the study died or were referred for further care. Almost all patients received some type of medication during their clinic visit (98.2%). Antibiotics were given to 38.6% of patients, and virtually all patients received pain or fever relief (96.5%). However, no anti-malarials were prescribed., Conclusions: Mobile clinics provide important health care where access to care is limited. Although rapid tests have guided appropriate treatment, challenges remain when a patient's presenting complaint is less well defined. In rural areas of southern Malawi, simple diagnostics are needed to guide treatment decisions., (© 2020 The College of Medicine and the Medical Association of Malawi.)

Concern exists in Europe about the possibility of importation of infectious diseases due to the recent influx of migrants and refugees after 2011. In this retrospective 6-year study, we examined the epidemiology of fever of unknown origin (FUO) in Greece over the past years. Forty-eight patients with classical FUO were included. The proportion of infectious causes of FUO (29.2%) was similar to previous studies in Greece and all infections were endemic to the area. Disease-related mortality was 12.5% and no deaths due to infection were recorded. In conclusion, none of the diagnosed infectious causes of FUO raised concerns about the possibility of imported diseases or pathogens. These results re-inforce the perception that migrants and refugees are not carriers of communicable diseases that can cause public health problems to European countries., Competing Interests: Conflicts of interest Authors declare that they have no conflicts of interest in relation to this study., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Fever of unknown origin refers to a prolonged fever with an unknown cause despite adequate medical evaluations. This condition often leads to unnecessary extensive laboratory work-ups and antimicrobial therapies. The atypical presentations often cause a delayed diagnosis and an improper treatment with an increased morbidity rate. In cardiac surgical patients, fever of unknown origin remains an intriguing problem during the diagnostic process of cardiac surgical diseases. Cardiac myxoma or aortic dissection are often misdiagnosed when patients present with fever of unknown origin as an onset symptom. Under such circumstances, medical examinations by echocardiography and chest computed tomography, particularly fluorodeoxyglucose-positron emission tomography/computed tomography, have been proved crucial for early diagnosis. A better understanding of the clinical features of cardiac surgical disorders presenting with fever of unknown origin would facilitate early diagnosis of fever of unknown origin. A further decision-making of prompt treatment of choices of a cardiac operation is important for improving patients' outcomes., Competing Interests: Author declares no conflict of interest., (© 2019 Yuan Published by IMR press.)

Introduction: Fever of unknown origin (FUO) with pulmonary lesions is a common syndrome in respiratory diseases, which can be caused by infection, cancer, connective tissue disease and other rare diseases of South China. In patients with FUO associated with pulmonary lesions, pathogeny should be identified and followed by an appropriate treatment strategy., Objective: This study aimed to investigate the etiological distribution and clinical features of FUO with pulmonary lesions and to analyze the efficiency of different diagnostic methods for certain disease categories., Methods: Patients hospitalized at the Guangzhou Institute of Respiratory Health from July 2012 to December 2016 who had fever ≥38.3°C that lasted ≥21 days, in whom the chest X-ray or computed tomography (CT) revealed definite pulmonary infiltration, and for whom, despite being examined for a week, no definitive diagnosis could be made, were considered for this study., Results: A total of 104 patients were identified as having FUO with lung lesions, and 89.4% (93/104) patients were definitively diagnosed. Infectious disease was the most common cause (46.2%, 48/104). Histopathology was instrumental in the diagnosis of the causes of FUO with pulmonary manifestations, 47.3% (44/93) patients were diagnosed through histopathology, 35.4% (17/48) with infectious disease and 55.2% (16/29) with connective tissue diseases as the etiology were definitely diagnosed using histopathology., Conclusion: Most FUO with pulmonary lesions are identified during infections and autoimmune diseases. The most important diagnostic measure for FUO with pulmonary lesions is histopathology. Additionally, lung biopsy must be encouraged in multi-level hospitals in the future., (© 2019 John Wiley & Sons Ltd.)

The diagnosis and treatment of fever of unknown origin (FUO) are huge challenges to clinicians. Separating the etiologies of FUO into infectious and non-infectious disease is conducive to clinical physicians not only on making decisions rapidly concerning the prescription of suitable antibiotics but also on further analysis of the final diagnosis. In order to develop and validate a diagnostic tool to efficiently distinguish the etiologies of adult FUO patients as infectious or non-infectious disease, FUO patients from the departments of infectious disease and internal medicine in three Chinese tertiary hospitals were enrolled retrospectively and prospectively. By using polynomial logistic regression analysis, the diagnostic formula and the associated scoring system were developed. The variables included in this diagnostic formula were from clinical evaluations and common laboratory examinations. The proposed tool could discriminate infectious and non-infectious causes of FUO with an area under receiver operating characteristic curve (AUC) of 0.83, sensitivity of 0.80 and specificity of 0.75. This diagnosis tool could predict the infectious and non-infectious causes of FUO in the validation cohort with an AUC of 0.79, sensitivity of 0.79 and specificity of 0.70. The results suggested that this diagnostic tool could be a reliable tool to discriminate between infectious and non-infectious causes of FUO.

Background: Bone marrow biopsy (BMB) is an accepted investigation in fever of unknown origin (FUO) to uncover haematological malignancies, such as lymphoma, and sometimes infections. With the advance in imaging modalities, such as 18-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) to identify the focus of lymphoma, BMB may not contribute to the diagnosis when there are no other clinical features to suggest an underlying haematological disease., Aim: To investigate the utility of BMB in determining the cause of FUO, when there are no other indications for BMB., Methods: Medical records of adult patients who had BMB performed for FUO or febrile illness from 1 January 2005 to 31 December 2014 in four metropolitan tertiary hospitals in Melbourne, Australia were reviewed. Patients with other concurrent indications for BMB, known human immunodeficiency virus infection and previously diagnosed connective tissue diseases were excluded., Results: Seventy-three patients were included in the study. Fifty-one patients had a final diagnosis for fever (systemic inflammatory diseases, infective, malignancy or other) while 22 patients had no diagnoses. In only 10 patients (13.7%) did BMB contribute to the diagnosis, finding either malignancy or granulomata. However, all these diagnoses could have been made without BMB. Two patients with diffuse large B-cell lymphoma had normal BMB. FDG-PET was helpful in making a diagnosis in eight (25%) out of 32 patients., Conclusion: Performing BMB in patients with FUO and no other haematological abnormalities is of very limited value, and other investigations, such as FDG-PET, may be more likely to help establish a definitive diagnosis., (© 2019 Royal Australasian College of Physicians.)

Objectives: To document the current training, implementation and role of modern musculoskeletal imaging techniques: ultrasound, magnetic resonance imaging, computed tomography and positron emission tomography, among rheumatologists in the member countries of the EULAR., Methods: English-language questionnaires for each imaging modality developed by a EULAR task force were sent out to national and international scientific societies as well as imaging experts in the given modalities involved in research and/or training. The surveys were distributed via an online survey tool (SurveyMonkey). Simple descriptive and summary statistics were calculated from the responses., Results: More than 90% of ultrasound (US) experts reported the availability of a US unit in their department. Suspicion of rheumatoid arthritis and spondyloarthritides were the main clinical indications for performing US for diagnostic purposes. Suspicion of sacroiliitis and degenerative spine disease were the most common indications to perform magnetic resonance imaging (MRI) or computed tomography (CT) for diagnostic purposes, while positron emission tomography was mainly performed to diagnose large vessel vasculitis and to investigate fever of unknown origin. The reported percentage of rheumatologists performing US was highly variable, ranging from more than 80% in 6% of countries to less than 10% in 15% of countries. The majority of experts (77%) reported that their national rheumatology societies organise musculoskeletal US courses, while courses in MRI or CT organised by the national rheumatology societies were less commonly reported (29% and 8%, respectively)., Conclusions: Rheumatologists in Europe utilise modern imaging techniques; however, access to the techniques and training offered is varied., Competing Interests: Competing interests: None declared.

Background: Non-malarial febrile illnesses comprise of almost half of all fever presenting morbidities, among under-five children in sub-Saharan Africa. Studies have reported cases of prescription of antimalarial medications to these febrile under-fives who were negative for malaria. The treatment of these children with antimalarial medications increases incidences of antimalarial drug resistance as well as further morbidities and mortalities, due to failure to treat the actual underlying causes of fever., Aim: To identify clinical and demographic factors associated with treatment type (malarial/non-malarial) of non-malarial febrile illnesses (NMFI) in children aged ≤5 at the Kenyatta National Hospital in Nairobi, Kenya., Methods: A positivist epistemological approach, cross sectional descriptive study design was used. A structured questionnaire was used on a sample of 341 medical records of children aged ≤5 years to extract data on clinical examinations (recorded as yes or no), diagnostic test results, and demographic data on the child's sex and age. Descriptive and inferential analysis was applied to the data., Results: Prescription of antimalarial drugs despite negative microscopy results was found in 44 (12.9%) of the children, with mortality reported in 48 (14.1%). Assessment of respiratory distress was 0.13 (0.03,0.58) times associated with less likelihood of prescribing an antimalarial in those with a negative microscopy. A male patient was 0.21 (0.05,0.89) times less likely to receive an intravenous antimalarial after a negative microscopy. Patients aged ˂1 with a negative microscopy result were more likely to receive an antimalarial than older children., Conclusion: There is a need to eliminate incorrect treatment of NMFI with antimalarial medication, while ensuring correct diagnosis and treatment of the specific illness occurs. This requires strengthening and adherence to diagnostic and treatment guidelines of febrile illnesses in under-fives, consequently reducing morbidities and mortalities associated with inadequate management of NMFIs., Competing Interests: The authors have declared that no competing interests exist.

Background: The outcome of Kawasaki disease (KD) depends on cardiovascular complications (CVCs)., Objectives: This study aimed to explore diagnostic features and CVCs in Tunisian patients with KD., Methods: In total, 33 Tunisian patients (age, 2.9 ± 2.2 years) fulfilling the diagnosis criteria of KD, were retrospectively reviewed. Nonparametric tests were used to compare the two groups with regards to coronary complications (CCs)., Results: Diagnosis of KD was established at day 11 ± 5.1 from the beginning of the fever. Apyrexia was obtained in an average of 29 h after completion of intravenous immunoglobulin. CVCs were identified in 52% of cases: CC in 15 patients (giant aneurysm >8 mm in five patients) and non-CCs in 6 patients (severe in three patients). CCs were more frequently associated with the male sex (p = 0.037), fever lasting >8 days (p = 0.028) and longer time to apyrexia (p = 0.031)., Conclusion: In Tunisia, better knowledge and monitoring of KD are warranted., (© The Author(s) [2018]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Temporal artery biopsy (TAB) is useful in assisting with giant cell arteritis (GCA) diagnosis but lacks sensitivity. The aim of our study was to assess the diagnostic impact of TAB histology in patients with suspected GCA on hospital admission., Methods: A prospectively maintained database was queried for all TABs performed between 1-1-2000 until 31-12-2017 at the University Hospital of Ioannina. Thus, inclusion criteria were made on the grounds of every patient that underwent a TAB during the above-mentioned period, regardless of demographic, clinical and laboratory data., Results: Two hundred forty-five TABs were included (149 females and 96 males), with a mean age of 64.5 (±3.5) years. The mean symptoms duration until admission to the hospital was 8.6 (±1.3) weeks and all had elevated acute phase reactants on admission. The reasons of admission were fever of unknown origin (FUO) in 114 (46.5%) patients, symptoms of polymyalgia rheumatica (PMR) in 84 (34.3%), new headache in 33 (13.5%), anemia of chronic disease (ACD) in 8 (3.32%) and eye disturbances in 6 (2.5%) patients. Positive results were found in 49 (20%) TABs. More specifically, in 14% of patients with FUO, 21% in those with PMR, while in patients with a new headache the percentage was 27%. Finally, 5 out of 6 (83.3%) of patients with ocular symptoms and only one (12.5%) of those suffering from ACD. Visual manifestations and FUO are correlated with a positive TAB., Conclusion: It seems that TAB is useful in assisting with GCA diagnosis, but lacks sensitivity., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Late Diagnosis (LD) of Human Immunodeficiency Virus (HIV) infection (CD4 lymphocytes <350/μl at diagnosis of the disease), deteriorates the condition of those affected and increases the probability of transmission. The objective of the present study was to analyse the prevalence of LD, to identify missed diagnostic opportunities (MDO) and to find out which level of the health care delivery system they took place., Methods: Retrospective, observational and descriptive study of the population diagnosed with infection of HIV/AIDS in the period 2011-2015 in Aragon. MDO were identified during the 3 years prior to diagnosis of the disease in all levels of the health care delivery system as well as frequentation of consultations. The indicator conditions (IC) that generated more MDO were analysed according to the latest recommendations for early diagnosis of HIV in the health care setting., Results: 435 newly diagnosed HIV/AIDS cases were analysed. 45.1% were diagnosed in Primary Healthcare (PH). 49.4% presented criteria of LD and 61.1% were infected through heterosexual contact. The majority of MDO (68.5%) were given in PH. The IC that generated the most MDO were seborrheic dermatitis/exanthema (19.4%) and fever of unknown origin (10.3%). However, the IC that were associated with higher LD were pneumonia acquired in the community and unjustified weight loss., Conclusion: In Aragon, prevalence of LD is high, the main route of infection is heterosexual and most of MDO go unnoticed in PH. The dissemination of current guidelines for requesting IC guided HIV testing and HIV screening across the preoperative period will result in an effective measure to decrease the LD., (Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

In 2013, the Guinean health authority had to reorganise and run a national response against malaria as a priority. The review of the National Strategic Plan to fight malaria in Guinea was carried out and one of its critical components was the prevention and rapid management of fever (RMF) attributable to malaria in children. The study reports on the demographic and health determinants of this rapid management in children under 5. The participants were 4786 children from 2874 representative households. RMF was defined in terms of recourse to primary care. The recourse was defined by child's reference for the treatment of fever which led or not to treatment of malaria. We found that 1491 children (31.2%) had a bout of fever within the 2 weeks that preceded the survey. The prevalence of malaria was 45.4% among those children who have a bout of fever. The recourse to traditional healers was estimated at 9.6% and the use of health facilities was estimated at 71.5%. Overall, 74.9% of children with fever received treatment within the recommended timeliness (24 h), with regional disparity in this rapid response. The high proportion of recourse to traditional healers is still a matter of concern. New control and prevention strategies should be extended to traditional healers for their training and involvement in directing febrile children to health facilities.

Background: Tuberculosis (TB), especially extrapulmonary tuberculosis (EPTB), is an important cause of fever of unknown origin (FUO) in TB-burdened areas. Little information is known about patients with EPTB with clinical features presenting as FUO and about the factor of delaying the diagnosis., Methods: We retrospectively analyzed EPTB patients who were referred with FUO at 3 university-affiliated hospitals over 8 years (2010-2017). The subjects were assigned to groups of early diagnosis and delayed diagnosis within 3 days of an initial comprehensive evaluation from the referral. Clinical and laboratory variables were compared between the groups., Results: A total of 95 patients with febrile EPTB were included. Localizing symptoms and/or signs suggestive of anatomy were identified in 62.1% of the patients. Concurrent lung involvement by TB was presented by 49.5% (47/95) of the patients, and only 23.4% of them showed typical findings of pulmonary TB on simple chest X-ray. Most of the patients showed abnormal lesions on cross-sectional CT (98.9%) and MRI (100%). The clinical variables and blood test results of patients were not significantly different between the two groups. The less typical imaging finding of EPTB on CT (38.5% vs. 79.0%) and MRI (37.5% vs. 79.0%) in the delayed diagnosis group was a risk factor for delayed diagnosis., Conclusion: Febrile EPTB referred as FUO showed nonspecific clinical manifestations. The active application of cross-sectional imaging tests according to clinical clues or randomly in the absence of local manifestations, combined with invasive diagnostic approaches even for atypical presentations may lead to an earlier diagnosis of febrile EPTB.

Introduction: Immediate empirical antibiotic therapy is mandatory in febrile chemotherapy-induced neutropenia, but its optimal duration is unclear, especially in patients with fever of unknown origin (FUO)., Objectives: The primary objective of this 20-month prospective observational study was to evaluate the feasibility and safety of short-term antibiotic treatment in afebrile or febrile patients exhibiting FUO, irrespective of their neutrophil count. The secondary objective was to describe the epidemiology of all episodes of febrile neutropenia., Methods: In the first phase of the study, empirical antibiotic therapy in FUO patients was stopped after 48 h of apyrexia, in accordance with European Conference on Infections in Leukaemia guidelines (n = 45). In the second phase of the study, antibiotics were stopped no later than day 5 for all FUO patients, regardless of body temperature or leukocyte count (n = 37)., Results: Two hundred and thirty-eight cases of febrile neutropenia in 123 patients were included. Neither the composite endpoint (p = .11), nor each component (in-hospital mortality (p = .80), intensive care unit admission (p = 0.48), relapse of infection ≤48 h after discontinuation of antibiotics (p = .82)) differed between the two FUO groups. Violation of protocol occurred in 17/82 episodes of FUO without any major impact on statistical results. Twenty-six (57.3%) and 22 (59.5%) FUO episodes did not relapse during hospital-stay (p = 1), and nine (20%) and five (13.5%) presented another FUO, respectively. One hundred and fifty-six episodes of febrile neutropenia (65.5%) were clinically or microbiologically documented, including 85 bacteremia., Conclusions: These results suggest that early discontinuation of empirical antibiotics in FUO is safe for afebrile neutropenic patients.

Objective: To study the incidence of rickettsial infection in pyrexia of unknown origin (PUO) patients. To promote awareness and index of suspicion among clinicians for rickettsial infection., Methods: Out of numerous patients who came to a tertiary care hospital in Delhi with fever, sera of 22 patients in whom no diagnosis could be made after basic investigations and cultures were subjected to Weil Felix (WF) test., Results: Out of 22 patients, 14 patients tested reactive by WF test. 6 patients each were positive for OX-2 and OX-K antigens. In 3 patients, OX-2 antigen was positive with OX-19 antigen and in 3 with OX-K antigen. One patient showed a positive titer with all three Proteus antigens. All these patients responded well to standard treatment of rickettsial infections., Conclusion: Rickettsial diseases are one of the many causes of PUO cases. Even if advanced diagnostic facilities are not available, simple and easy to perform WF test can aid in the diagnosis of rickettsial infections., (© Journal of the Association of Physicians of India 2011.)

In 30-50% of patients with fever of unknown origin (IUO) no explanation for the fever can be found. Prognosis and effects of empirical treatment of these patients are largely unknown.With this retrospective, questionnaire based corort study in all unexplained FUO patients in an expert center between 2003 and 2014 we studied mortality and outcome.In 131 of 274 FUO patients, FUO remained unexplained. Ninety-nine of them responded to the long-term follow up questionnaire. Adter a median duration of follow-up of 60 months, spontaneous remission of fever occured in 47.3%. Empirical treatment was effective in 66.7% of patients. Mortality was 6.9%. The cause of death was considered not to be related to the febrile disease in five out of six patients. Ten out of 99 responders reported to have received a final explanation for FUO after evaluation in the expertise center, but this diagnosis could not be confirmed in six cases and was considered to be an unlikely explanation for FUO in four out of six cases.We conclude that mortality in unexplained FUO is low en mostly unrelated to the febrile disease. Spontaneous resolution of fever is common. Empirical treatment prescribed by an expert physician is often effective, but should be avoided untill all diagnostic possibilities have been exhaused.

Outbreak investigation is a key component of public health training. A good outbreak investigation can go beyond determining the causative agent by recommending policies to be formulated by policy makers. This case study simulates a real-life investigation of pyrexia of unknown origin in Shamva District, Zimbabwe, during the period of September to October 2015. It aims at reinforcing principles and skills taught in class on outbreak investigation, study design and policy initiation. The target audience for the case study is Field Epidemiologists at their advanced level of training. It is expected to be completed in approximately 2 hours. General instructions: ideally, 1 to 2 facilitator(s) is/are required to facilitate the case study for 10 to 20 participants. The facilitator should request participants to read a paragraph out loud, going around the room to give each participant a chance to read. When the participant reads a question, the facilitator encourages all participants to engage in discussions, perform calculations, and draw graphs among other tasks. The facilitators request the participants to play different roles or take different sides in answering a question. As a result, participants learn from each other, not just from the facilitators.

Aim: We evaluated the diagnosis, risk stratification and management of febrile infants under three months of age who presented to an Israeli paediatric emergency room (ER)., Methods: This retrospective study enrolled all febrile infants examined in the paediatric ER of Soroka Medical Center during 2010-2013. The patients were classified into low-risk and high-risk subgroups and compared by age and ethnicity., Results: Overall, 2251 febrile infants (60.5% of Bedouin and 34.4% of Jewish ethnicity) were enrolled. Hospitalisation rates were higher among Bedouin vs. Jewish infants (55 vs. 39.8%, p < 0.001). Fever without localising signs was diagnosed in 1028 (45.6%) infants and 499 (48.5%) were hospitalised; 26% were stratified as high-risk and 74% as low-risk. Bedouin infants rates were more likely to be at high-risk (p = 0.001) and hospitalised (p < 0.001) than Jewish infants. With regard to low-risk infants, the incidence rates were higher before two months than two to three months of age (73.3 vs. 59%, p < 0.001), as were the hospitalisation rates (46.3 vs. 20.1%, p < 0.001). No differences were recorded for the hospitalisation rates of Bedouin and Jewish infants between the three daily shifts., Conclusion: Major differences were recorded in hospitalisation rates, risk stratification and management of Bedouin and Jewish infants with fever without localising signs., (©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Fever of unknown origin (FUO) is a well-known pediatric presentation. The primary studies determining the causes of prolonged fever in children were performed 4 decades ago, before major advances in laboratory and diagnostic testing. Given that the distribution of diagnosed causes of adult FUO has changed in recent decades, we hypothesized that the etiology of FUO in children has concordantly changed and also may be impacted by a definition that includes a shorter required duration of fever., Methods: A single-center, retrospective review of patients 6 months to 18 years of age admitted to the North Carolina Children's Hospital from January 1, 2002, to December 21, 2012, with an International Classification of Diseases, Ninth Revision diagnosis of fever, a documented fever duration >7 days before admission, and a previous physician evaluation of each patient's illness., Results: A total of 1164 patients were identified, and of these, 102 met our inclusion criteria for FUO. Etiologic categories included "infectious" (42 out of 102 patients), "autoimmune" (28 out of 102 patients), "oncologic" (18 out of 102 patients), and "other" or "unknown" (14 out of 102 patients). Several clinical factors were statistically and significantly different between etiologic categories, including fever length, laboratory values, imaging performed, length of stay, and hospital costs., Conclusions: Unlike adult studies, the categorical distribution of diagnoses for pediatric FUO has marginally shifted compared to previously reported pediatric studies. Patients hospitalized with FUO undergo prolonged hospital stays and have high hospital costs. Additional study is needed to improve the recognition, treatment, and expense of diagnosis of prolonged fever in children., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

This descriptive study evaluated 49 children with fever lasting for more than 7 days at a tertiary hospital in urban Mumbai. Etiologic diagnosis could be established in 88% of the cases. Infections were the causein 34 (79%)patients, 6 (14%) were diagnosed as collagen vascular diseases, and 3 (7%) had other cause.

Background: Scrub typhus is lesser known cause of fever of unknown origin in India. Even if there have been reports documenting the prevalence of scrub typhus in different parts of India, it is still an unknown entity, and clinicians usually do not consider it as differential diagnosis. The present study was performed to document the prevalence of scrub typhus among febrile patients in western part of Uttar Pradesh and to assess the clinical profile of infected patients on the one hand and knowledge, attitude, and practices among clinicians on the other., Materials and Methods: A total of 357 adult patients with fever of more than 5-day duration were recruited. All patients underwent complete physical examination, and detailed clinical history was elicited as per predesigned pro forma. After primary screening to rule out malaria, enteric fever, and leptospirosis infection, secondary screening for scrub typhus was done by rapid screen test and IgM ELISA., Results: Scrub typhus infection was positive in 91 (25.5%) cases. The most common symptoms among the patients were fever (100%), pain in abdomen (79.1%), pedal edema 56 (61.5%), rash 44 (48.3%), headache 44 (48.3%), vomiting 42 (46.1%), constipation 33 (36.2%), cough 28 (30.7%), and lymphadenopathy 20 (21.9%). The median values of interleukin-8, interferon-gamma, and tumor necrosis factor-alpha in healthy controls were 15.54 pg/ml, 7.77 pg/ml, and 54.1 pg/ml, respectively, while the median values of these cytokines in scrub typhus-positive patients were 21.04 pg/ml, 8.74 pg/ml, and 73.8 pg/ml, respectively., Conclusion: Our results highlight that scrub typhus infection is an important cause of pyrexia of unknown origin, and active surveillance is necessary to assess the exact magnitude and distribution of the disease., Competing Interests: There are no conflicts of interest

Fever may be the only clinical symptom at the onset of infection in neutropenic cancer patients undergoing myelosuppressive chemotherapy. A prompt and evidence-based diagnostic and therapeutic approach is mandatory. A systematic search of current literature was conducted, including only full papers and excluding allogeneic hematopoietic stem cell transplant recipients. Recommendations for diagnosis and therapy were developed by an expert panel and approved after plenary discussion by the AGIHO. Randomized clinical trials were mainly available for therapeutic decisions, and new diagnostic procedures have been introduced into clinical practice in the past decade. Stratification into a high-risk versus low-risk patient population is recommended. In high-risk patients, initial empirical antimicrobial therapy should be active against pathogens most commonly involved in microbiologically documented and most threatening infections, including Pseudomonas aeruginosa, but excluding coagulase-negative staphylococci. In patients whose expected duration of neutropenia is more than 7 days and who do not respond to first-line antibacterial treatment, specifically in the absence of mold-active antifungal prophylaxis, further therapy should be directed also against fungi, in particular Aspergillus species. With regard to antimicrobial stewardship, treatment duration after defervescence in persistently neutropenic patients must be critically reconsidered and the choice of anti-infective agents adjusted to local epidemiology. This guideline updates recommendations for diagnosis and empirical therapy of fever of unknown origin in adult neutropenic cancer patients in light of the challenges of antimicrobial stewardship.

Introduction: Infectious agent when enters in the host results in febrile illness. This may lead to increase in morbidity or even mortality in undiagnosed/untreated cases. There are many aetiological agents which lead to acute febrile illness. Among these aetiological agents, important is bacterial or viral aetiology., Objective: The objective of this study is: (i) To know the aetiological agents responsible for acute undifferentiated febrile illness (AUFI) by serological test or by bacterial culture and (ii) To know the clinical profile of AUFI., Methodology: A total of 270 patients were enroled in the study with a history of AUFI admitted in medicine and paediatric department from January 2015 to November 2016 of tertiary care hospital of central India. Blood sample was collected for blood culture, clot culture and serological tests for immunochromatographic tests (ICTs) and ICT-positive results were confirmed by respective enzyme-linked immunosorbent assay (ELISA). All negative serum samples by immunochromatography were retested for disease-specific ELISA as scrub typhus, dengue and leptospirosis., Results: Out of 270 patients, 127 (47%) were of scrub typhus, 33 (12%) were malaria cases, 47 (17.40%) were dengue, 12 (4%) were enteric fever, 5 (2%) were leptospirosis, undiagnosed were 18 (6.66%) and other infections (viz viral, urinary tract infection, upper and lower respiratory tract infection and acute gastroenteritis) accounts for 28 (10.37%) cases. We have also noticed that there was co-infection of scrub typhus and dengue, leptospirosis and scrub typhus., Conclusion: It is important to know the cause and clinical profile of AUFIs for their proper management also it will help to prevent morbidity and mortality in AUFI cases.

Background: Recently, Balkan virus (BALKV, family Phenuiviridae, genus Phlebovirus) was discovered in sand flies collected in Albania and genetically characterised as a member of the Sandfly fever Naples species complex. To gain knowledge concerning the geographical area where exposure to BALKV exists, entomological surveys were conducted in 2014 and 2015, in Croatia, Bosnia and Herzegovina (BH), Kosovo, Republic of Macedonia and Serbia., Results: A total of 2830 sand flies were trapped during 2014 and 2015 campaigns, and organised as 263 pools. BALKV RNA was detected in four pools from Croatia and in one pool from BH. Phylogenetic relationships were examined using sequences in the S and L RNA segments. Study of the diversity between BALKV sequences from Albania, Croatia and BH showed that Albanian sequences were the most divergent (9-11% [NP]) from the others and that Croatian and BH sequences were grouped (0.9-5.4% [NP]; 0.7-5% [L]). The sand fly infection rate of BALKV was 0.26% in BH and 0.27% in Croatia. Identification of the species content of pools using cox1 and cytb partial regions showed that the five BALKV positive pools contained Phlebotomus neglectus DNA; in four pools, P neglectus was the unique species, whereas P. tobbi DNA was also detected in one pool., Conclusions: We report here (i) the first direct evidence that the Balkan virus initially described in coastal Albania has a much wider dissemination area than originally believed, (ii) two real-time RT-PCR assays that may be useful for further screening of patients presenting with fever of unknown origin that may be caused by Balkan virus infection, (iii) entomological results suggesting that Balkan virus is likely transmitted by Phlebotomus neglectus, and possibly other sand fly species of the subgenus Larroussius. So far, BALKV has been detected only in sand flies. Whether BALKV can cause disease in humans is unknown and remains to be investigated.

Aortic dissection is the most devastating sequela of thoracic aortic disorder. Patients with acute aortic dissection typically manifest as an acute onset of severe chest pain, but occasionally present with atypical symptoms including fever of unknown origin. A total of 50 patients from 41 articles based on a complete literature retrieval were included in this study. More patients had a fever prior to pain. The time to presentation was 40.7 ± 105.6 days, the time to diagnosis was 52.9 ± 110.1 days, and the time to surgery/intervention was 1.8 ± 5.6 days. The patients' temperature on admission was 38.2 ± 0.6 °C and the maximal temperature recorded was 38.8 ± 0.4 °C. Laboratory findings showed increased white blood cell counts, cardiac enzymes, and inflammatory biomarkers. More pronounced laboratory findings of the infectious type than the inflammatory type aortic dissection could be helpful in the differential diagnosis. Half of patients warrant aortic repair with or without valve replacement, less than half of patients were conservatively managed, and a few were interventionally treated or were being followed up. The mortality rate was 9.5 %. Physicians should always bear in mind aortic dissection when patients present with fever of unknown origin particularly in those without chest pain. Laboratory findings may offer inflammatory evidence for the diagnosis. An early diagnosis as well as subsequent treatment is indispensable for patients' outcomes.

To investigate the etiology and differential diagnoses of patients with systemic lupus erythematosus (SLE) and fever of unknown origin (FUO). From January 2012 to December 2014, a total of 928 SLE patients were admitted to Peking Union Medical College Hospital.Only 50 patients were combined with FUO (5.4%). The most common reason of fever was caused by infections(33 cases, 66.0%), including bacterial infection in 17 cases with 5 tuberculosis, viral infection in 11 cases, and fungal infection in 5 cases.The second reason offever was due to poor disease control or recurrence in 17 patients (34.0%). No fever was caused by malignant tumor.When clinical data was compared between 17 non-infected patients versus 33 infected patients, C reactive protein and procalcitonin in the infected group were significantly higher than those in the non-infected group.In SLE patients combined with FUO, infection is the most common etiology which is necessary to be paid attention to.