Incidence and outcomes of fever of unknown origin after kidney transplant in the modern era.

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.

Integrating Medical Domain Knowledge for Early Diagnosis of Fever of Unknown Origin: An Interpretable Hierarchical Multimodal Neural Network Approach.

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.

Structured diagnostic scheme clinical experience sharing: a prospective study of 320 cases of fever of unknown origin in a tertiary hospital in North China.

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.

Classical fever of unknown origin in 21 countries with different economic development: an international ID-IRI study.

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.

Adult-onset Still's disease and fever of unknown origin in India.

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.

Human brucellosis and fever of unknown origin.

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.

Pyrexia of unknown origin and its aetiology in Pakistan.

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.

Prospective Studies Comparing Structured vs Nonstructured Diagnostic Protocol Evaluations Among Patients With Fever of Unknown Origin: A Systematic Review and Meta-analysis.

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.

Fever of unknown origin (FUO) in children: a single-centre experience from Beijing, China.

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 χ2 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.

Etiologies of fever of unknown origin in HIV/AIDS patients, Hanoi, Vietnam.

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/mm3 and ≥ 50 cells/mm3. 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/mm3. 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/mm3. 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/mm3. 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.

Fever of Unknown Origin and Incidence of Cancer.

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.

Fever of Unknown Origin in Older Adults: A Prospective Observational Study from North India.

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.

Poor outcome and high prevalence of invasive fungal infections in patients with adult T-cell leukemia/lymphoma exposed to zidovudine and interferon alfa.

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.

[Febrile syndrome in children younger than 29 days]. / Síndrome febril en niños menores de 29 días.

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.

Fever of unknown origin (FUO) on a land on cross-roads between Asia and Europa; a multicentre study from Turkey.

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.

Comparison of clinical characteristics of Zika and dengue symptomatic infections and other acute illnesses of unidentified origin in Mexico.

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.

Nursing management at a Chinese fever clinic during the COVID-19 pandemic.

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.

Aetiology of pyrexia of unknown origin in north India.

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.

A 14-day follow-up of adult non-malarial fever patients seen by mobile clinics in rural Malawi.

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.