Pre-pandemic antibodies screening against SARS-CoV-2 and virus detection among children diagnosed with eruptive fevers.

OBJECTIVES: This study aims to assess the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibodies against the spike (S) and nucleocapsid (NP) proteins, as well as neutralizing antibodies against the receptor-binding domain (RBD). Additionally, it aims to detect viral RNA of SARS-CoV-2 in pre-pandemic archival pediatric specimens collected before the announcement of the COVID-19 pandemic spread on March 20th, 2020, in Morocco. The objective is to investigate the existence of pre-pandemic immunity to SARS-CoV-2. METHODS: We conducted a cross-sectional study, to analyze IgG antibody levels in a cohort of 106 pre-pandemic pediatric participants. Using an indirect enzyme-linked immunosorbent assay (ELISA), we measured the IgG levels against the S and NP proteins of SARS-CoV-2. Additionally, we staged a competitive ELISA assay to evaluate the neutralizing capability of these antibodies. We used reverse transcription polymerase chain reaction (rRT-PCR) to detect viral NP and ORF1ab genes of SARS-CoV-2 in oropharyngeal swabs. Moreover, we conducted on the same specimens a multiplexed RT-PCR to detect RNA of the most common 27 pathogens involved in lower respiratory tract infections. RESULTS: Among the 106 serum samples, 13% (nn = =14) tested positive for SARS-CoV-2 IgG antibodies using ELISA. Temporal analysis indicated varying IgG positivity levels across 2019. Neutralizing antibodies were found in 21% of the 28 samples analyzed, including two with high inhibition rates (93%). The SARS-CoV-2 RNA was detected using rRT-PCR in 14 samples. None of the samples tested positive for the other 27 pathogens associated with lower respiratory tract infections, using multiplexed RT-PCR. CONCLUSION: Our study addresses the possibility, that COVID-19 infections occurred in Morocco before the recognized outbreak. On the other hand, some of the cases might reflect cross-reactivity with other coronaviruses or be influenced by previous viral exposures or vaccinations. Understanding these factors is crucial to comprehending pediatric immune responses to newly emerging infectious diseases.

Safely Doing Less for Febrile Infants: Reviewing Management in the Setting of the 2021 American Academy of Pediatrics Clinical Practice Guideline.

For more than 4 decades, pediatricians have sought the best practices for effectively managing well-appearing young febrile infants. In 2021, the American Academy of Pediatrics released a clinical practice guideline for the management of well-appearing febrile infants aged 8 to 60 days. The guideline incorporates advancements in testing, such as biomarkers and diagnostic testing in the setting of changing epidemiology, to help risk stratify infants in the newly formed group age 22 to 28 days as well as the group age 29 to 60 days. The new guideline uses inflammatory markers (procalcitonin, C-reactive protein, absolute neutrophil count, and a temperature >38.4°C) to identify infants at low risk for invasive bacterial infection who can potentially avoid the invasive procedures of lumbar puncture, hospitalization, and broad-spectrum antimicrobials. Because of continued ambiguity, incorporating shared decision-making with families in the care of these infants will be important, as will ongoing clinical research to better inform future practice. [Pediatr Ann. 2024;53(6):e202-e207.].

Multi-criteria decision analysis method for differential diagnosis of tropical febrile diseases.

This paper employs the Analytical Hierarchy Process (AHP) to enhance the accuracy of differential diagnosis for febrile diseases, particularly prevalent in tropical regions where misdiagnosis may have severe consequences. The migration of health workers from developing countries has resulted in frontline health workers (FHWs) using inadequate protocols for the diagnosis of complex health conditions. The study introduces an innovative AHP-based Medical Decision Support System (MDSS) incorporating disease risk factors derived from physicians' experiential knowledge to address this challenge. The system's aggregate diagnostic factor index determines the likelihood of febrile illnesses. Compared to existing literature, AHP models with risk factors demonstrate superior prediction accuracy, closely aligning with physicians' suspected diagnoses. The model's accuracy ranges from 85.4% to 96.9% for various diseases, surpassing physicians' predictions for Lassa, Dengue, and Yellow Fevers. The MDSS is recommended for use by FHWs in communities lacking medical experts, facilitating timely and precise diagnoses, efficient application of diagnostic test kits, and reducing overhead expenses for administrators.

Combining serum microRNAs and machine learning algorithms for diagnosing infectious fever after HSCT.

Infection post-hematopoietic stem cell transplantation (HSCT) is one of the main causes of patient mortality. Fever is the most crucial clinical symptom indicating infection. However, current microbial detection methods are limited. Therefore, timely diagnosis of infectious fever and administration of antimicrobial drugs can effectively reduce patient mortality. In this study, serum samples were collected from 181 patients with HSCT with or without infection, as well as the clinical information. And more than 80 infectious-related microRNAs in the serum were selected according to the bulk RNA-seq result and detected in the 345 time-pointed serum samples by Q-PCR. Unsupervised clustering result indicates a close association between these microRNAs expression and infection occurrence. Compared to the uninfected cohort, more than 10 serum microRNAs were identified as the combined diagnostic markers in one formula constructed by the Random Forest (RF) algorithms, with a diagnostic accuracy more than 0.90. Furthermore, correlations of serum microRNAs to immune cells, inflammatory factors, pathgens, infection tissue, and prognosis were analyzed in the infection cohort. Overall, this study demonstrates that the combination of serum microRNAs detection and machine learning algorithms holds promising potential in diagnosing infectious fever after HSCT.

Contributing Factors Affecting the Length of Hospital Stay among Febrile Patients with Omicron Reported in Suzhou.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has had global attention with regard to the urgent challenging threat to global public health. Currently, the novel Omicron variant is showing rapid transmission across the world, which appears to be more contagious than the previous variants of COVID-19. Early recognition of disease is critical for patients' prognosis. Fever is the most common symptom. We evaluated the clinical characteristics of febrile patients with COVID-19 reported in Suzhou and explored the predictors for a longer duration of hospitalization in febrile patients. METHODS: This retrospective study was carried out in 146 Omicron variant infected patients confirmed by nucleic acid tests in the Affiliated Infectious Hospital of Soochow University between February 13, 2022 and March 2, 2022. Data of febrile and afebrile laboratory-confirmed patients on hospital admission in Suzhou were collected and compared. According to the median length of stay (LOS), febrile cases were divided into short and long LOS groups. Then the predictive factors for a prolonged duration of hospitalization were analyzed using logistic regression methods. Receiver Operating Characteristic (ROC) Curve analysis was used to analyze the effectiveness of the risk factors for prolonged duration of hospitalization in febrile COVID-19 patients. RESULTS: Of the 146 discharged patients in our study, 112 patients (76.7%) caught a fever. Compared to afebrile Omicron patients, febrile patients showed a significantly longer duration of hospitalization (15.00 (5.80) vs. 13.00 (6.00), p = 0.002). Taking the median LOS (15 days) as the dividing point, 64 febrile cases were assigned to the short LOS group and the rest to the long LOS group. The long LOS group had a longer virus shedding duration than the short LOS group (18.42 ± 2.86 vs. 11.94 ± 2.50 days, p < 0.001). Compared to short LOS febrile patients, long LOS patients were older (44.88 ± 21.36 vs. 30.89 ± 17.95 years, p < 0.001) and showed a higher proportion of greater than 60 years old (33.3% vs. 9.4%, p = 0.002; Supplemental Table S2). Febrile patients with long LOS also showed a higher proportion of hypertension (25% vs. 6.3%, p = 0.005) and higher levels of cTnI (5.00 (3.00) vs. 4.00 (2.00) µg/L, p = 0.025). The multivariate analysis indicated that virus shedding duration (OR 2.369, 95% CI 1.684 - 3.333, p < 0.001) was the independent risk factor associated with long-term hospital stay in febrile patients with Omicron. Furthermore, ROC Curve analysis revealed that the area under the curve (AUC) for virus shedding duration to diagnose prolonged duration of hospitalization in febrile COVID-19 patients was 0.951 (95% CI 0.913 - 0.989). The cutoff point was set at 14.5 days. CONCLUSIONS: More than half of the non-severe patients exposed to the new Omicron variant had symptoms of fever. In total, 42.86% of the febrile patients were discharged within 15 days since hospital admission. Febrile Omicron cases took a longer duration of hospitalization compared to afebrile patients, and virus shedding duration (OR 2.369, 95% CI 1.684 - 3.333, p < 0.001) was probably a predictive factor for long-term hospital stays.

Unravelling the clinical heterogeneity of undefined recurrent fever over time in the European registries on Autoinflammation.

BACKGROUND: Systemic autoinflammatory disorders (SAIDs) represent a growing spectrum of diseases characterized by dysregulation of the innate immune system. The most common pediatric autoinflammatory fever syndrome, Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA), has well defined clinical diagnostic criteria, but there is a subset of patients who do not meet these criteria and are classified as undefined autoinflammatory diseases (uAID). This project, endorsed by PRES, supported by the EMERGE fellowship program, aimed to analyze the evolution of symptoms in recurrent fevers without molecular diagnosis in the context of undifferentiated AIDs, focusing on PFAPA and syndrome of undifferentiated recurrent fever (SURF), using data from European AID registries. METHODS: Data of patients with PFAPA, SURF and uSAID were collected from 3 registries including detailed epidemiological, demographic and clinical data, results of the genetic testing and additional laboratory investigations with retrospective application of the modified Marshall and PRINTO/Eurofever classification criteria on the cohort of PFAPA patients and preliminary SURF criteria on uSAID/SURF patients. RESULTS: Clinical presentation of PFAPA is variable and some patients did not fit the conventional PFAPA criteria and exhibit different symptoms. Some patients did not meet the criteria for either PFAPA or SURF, highlighting the heterogeneity within these groups. The study also explored potential overlaps between PFAPA and SURF/uAID, revealing that some patients exhibited symptoms characteristic of both conditions, emphasizing the need for more precise classification criteria. CONCLUSIONS: Patients with recurrent fevers without molecular diagnoses represent a clinically heterogeneous group. Improved classification criteria are needed for both PFAPA and SURF/uAID to accurately identify and manage these patients, ultimately improving clinical outcomes.

Assessment of fever screening at airports in detecting domestic passengers infected with SARS-CoV-2, 2020-2022, Okinawa prefecture, Japan.

BACKGROUND: While airport screening measures for COVID-19 infected passengers at international airports worldwide have been greatly relaxed, observational studies evaluating fever screening alone at airports remain scarce. The purpose of this study is to retrospectively assess the effectiveness of fever screening at airports in preventing the influx of COVID-19 infected persons. METHODS: We conducted a retrospective epidemiological analysis of fever screening implemented at 9 airports in Okinawa Prefecture from May 2020 to March 2022. The number of passengers covered during the same period was 9,003,616 arriving at 9 airports in Okinawa Prefecture and 5,712,983 departing passengers at Naha Airport. The capture rate was defined as the proportion of reported COVID-19 cases who would have passed through airport screening to the number of suspected cases through fever screening at the airport, and this calculation used passengers arriving at Naha Airport and surveillance data collected by Okinawa Prefecture between May 2020 and March 2021. RESULTS: From May 2020 to March 2021, 4.09 million people were reported to pass through airports in Okinawa. During the same period, at least 122 people with COVID-19 infection arrived at the airports in Okinawa, but only a 10 suspected cases were detected; therefore, the capture rate is estimated to be up to 8.2% (95% CI: 4.00-14.56%). Our result of a fever screening rate is 0.0002% (95%CI: 0.0003-0.0006%) (10 suspected cases /2,971,198 arriving passengers). The refusal rate of passengers detected by thermography who did not respond to temperature measurements was 0.70% (95% CI: 0.19-1.78%) (4 passengers/572 passengers). CONCLUSIONS: This study revealed that airport screening based on thermography alone missed over 90% of COVID-19 infected cases, indicating that thermography screening may be ineffective as a border control measure. The fact that only 10 febrile cases were detected after screening approximately 3 million passengers suggests the need to introduce measures targeting asymptomatic infections, especially with long incubation periods. Therefore, other countermeasures, e.g. preboarding RT-PCR testing, are highly recommended during an epidemic satisfying World Health Organization (WHO) Public Health Emergency of International Concern (PHEIC) criteria with pathogen characteristics similar or exceeding SARS-CoV-2, especially when traveling to rural cities with limited medical resources.

Facial and ocular thermal mapping in black-and-gold howler monkey (Alouatta caraya) by infrared thermography: An ex situ study.

BACKGROUND: This study used infrared thermography (IRT) for mapping the facial and ocular temperatures of howler monkeys, to determine parameters for the diagnosis of febrile processes. There are no published IRT study in this species. METHODS: Were evaluated images of a group of monkeys kept under human care at Sorocaba Zoo (São Paulo, Brazil). The images were recorded during 1 year, in all seasons. Face and eye temperatures were evaluated. RESULTS: There are statistically significant differences in face and eye temperatures. Mean values and standard deviations for facial and ocular temperature were respectively: 33.0°C (2.1) and 36.5°C (1.9) in the summer; 31.5°C (4.5) and 35.3°C (3.6) in the autumn; 30.0°C (4.3) and 35.6°C (3.9) in the winter; 30.8°C (2.9) and 35.5°C (2.1) in the spring. CONCLUSIONS: The IRT was effective to establish a parameter for facial and ocular temperatures of black-and-gold howler monkeys kept under human care.

Molecular and serological diagnosis of multiple bacterial zoonoses in febrile outpatients in Garissa County, north-eastern Kenya.

Bacterial zoonoses are diseases caused by bacterial pathogens that can be naturally transmitted between humans and vertebrate animals. They are important causes of non-malarial fevers in Kenya, yet their epidemiology remains unclear. We investigated brucellosis, Q-fever and leptospirosis in the venous blood of 216 malaria-negative febrile patients recruited in two health centres (98 from Ijara and 118 from Sangailu health centres) in Garissa County in north-eastern Kenya. We determined exposure to the three zoonoses using serological (Rose Bengal test for Brucella spp., ELISA for C. burnetti and microscopic agglutination test for Leptospira spp.) and real-time PCR testing and identified risk factors for exposure. We also used non-targeted metagenomic sequencing on nine selected patients to assess the presence of other possible bacterial causes of non-malarial fevers. Considerable PCR positivity was found for Brucella (19.4%, 95% confidence intervals [CI] 14.2-25.5) and Leptospira spp. (1.7%, 95% CI 0.4-4.9), and high endpoint titres were observed against leptospiral serovar Grippotyphosa from the serological testing. Patients aged 5-17 years old had 4.02 (95% CI 1.18-13.70, p-value = 0.03) and 2.42 (95% CI 1.09-5.34, p-value = 0.03) times higher odds of infection with Brucella spp. and Coxiella burnetii than those of ages 35-80. Additionally, patients who sourced water from dams/springs, and other sources (protected wells, boreholes, bottled water, and water pans) had 2.39 (95% CI 1.22-4.68, p-value = 0.01) and 2.24 (1.15-4.35, p-value = 0.02) times higher odds of exposure to C. burnetii than those who used unprotected wells. Streptococcus and Moraxella spp. were determined using metagenomic sequencing. Brucellosis, leptospirosis, Streptococcus and Moraxella infections are potentially important causes of non-malarial fevers in Garissa. This knowledge can guide routine diagnosis, thus helping lower the disease burden and ensure better health outcomes, especially in younger populations.

[Early diagnostic value of Presepsin in sepsis: a prospective study on a population with suspected sepsis in fever clinics].

OBJECTIVE: To analyze the early diagnostic value of plasma soluble cluster of differentiation 14 subtype (sCD14-ST, Presepsin) in sepsis in a population with suspected sepsis in fever clinic. METHODS: A prospective observational study was conducted. The patients admitted to the fever clinic of Beijing Chaoyang Hospital from April to December 2022 were enrolled as the study objects. According to sequential organ failure assessment (SOFA) score, the patients were divided into low SOFA score group (SOFA score ≤3) and high SOFA score group (SOFA score > 3). Venous blood was collected at the time of admission. The level of plasma Presepsin was detected by chemiluminescence enzyme-linked immunoassay. The level of plasma procalcitonin (PCT) was detected by enzyme-linked immunofluorescence method. The level of C-reactive protein (CRP) was detected by scattering turbidimetry. White blood cell count (WBC) and neutrophil count (NEUT) were measured by automatic blood cell analyzer. For patients with fear of cold or chills, venous blood of upper limbs was taken for blood culture at the time of admission. The differences in inflammatory biomarkers were compared between the two groups. Binary multivariate Logistic regression analysis was used to screen the early risk factors of sepsis in fever outpatients with suspected sepsis. Receiver operator characteristic curve (ROC curve) was drawn to investigate the early diagnostic value of Presepsin and other inflammatory markers in sepsis, and to analyze the optimal cut-off value. RESULTS: A total of 149 fever outpatients with suspected sepsis were enrolled, including 92 patients with low SOFA score and 57 patients with high SOFA score. Plasma PCT and Presepsin levels in the high SOFA score group were significantly higher than those in the low SOFA score group [PCT (µg/L): 0.77 (0.18, 2.02) vs. 0.22 (0.09, 0.71), Presepsin (ng/L): 1 129.00 (785.50, 1 766.50) vs. 563.00 (460.50, 772.25), both P < 0.01]. There was no significant difference in WBC, NEUT, CRP or positive rate of blood culture between the high and low SOFA score groups [WBC (×109/L): 11.32±5.47 vs. 11.14±5.29, NEUT (×109/L): 9.88±4.89 vs. 9.60±5.10, CRP (mg/L): 54.05 (15.95, 128.90) vs. 46.11 (19.60, 104.60), blood culture positivity rate: 42.3% (11/26) vs. 29.4% (10/34), all P > 0.05]. Multivariate Logistic regression analysis showed that Presepsin was an early risk factor for sepsis in suspected sepsis patients in fever clinics [odds ratio (OR) = 16.96, 95% confidence interval (95%CI) was 6.35-45.29, P = 0.000]. ROC curve analysis showed that the early diagnostic value of Presepsin in sepsis was significantly better than WBC, NEUT, CRP, PCT, and blood culture [the area under the ROC curve (AUC) and 95%CI: 0.832 (0.771-0.899) vs. 0.522 (0.424-0.619), 0.532 (0.435-0.629), 0.533 (0.435-0.632), 0.664 (0.574-0.753), 0.554 (0.458-0.650)]. When the optimal cut-off value of Presepsin was 646.50 ng/L, its sensitivity and positive predictive value were higher than those of WBC, NEUT, CRP, and PCT (sensitivity: 89.5% vs. 38.6%, 68.4%, 38.6%, 57.9%; positive predictive value: 64.6% vs. 44.9%, 44.3%, 47.8%, 55.9%). CONCLUSIONS: Plasma PCT and Presepsin have early diagnostic value for sepsis in suspected sepsis patients in fever clinics, and Presepsin is more sensitive than PCT and can be used as an early marker of sepsis.

Fever and Rash.

Infectious causes of fever and rash pose a diagnostic challenge for the emergency provider. It is often difficult to discern rashes associated with rapidly progressive and life-threatening infections from benign exanthems, which comprise the majority of rashes seen in the emergency department. Physicians must also consider serious noninfectious causes of fever and rash. A correct diagnosis depends on an exhaustive history and head-to-toe skin examination as most emergent causes of fever and rash remain clinical diagnoses. A provisional diagnosis and immediate treatment with antimicrobials and supportive care are usually required prior to the return of confirmatory laboratory testing.

Diagnostic accuracy of DPP Fever Panel II Asia tests for tropical fever diagnosis.

BACKGROUND: Fever is the most frequent symptom in patients seeking care in South and Southeast Asia. The introduction of rapid diagnostic tests (RDTs) for malaria continues to drive patient management and care. Malaria-negative cases are commonly treated with antibiotics without confirmation of bacteraemia. Conventional laboratory tests for differential diagnosis require skilled staff and appropriate access to healthcare facilities. In addition, introducing single-disease RDTs instead of conventional laboratory tests remains costly. To overcome some of the delivery challenges of multiple separate tests, a multiplexed RDT with the capacity to diagnose a diverse range of tropical fevers would be a cost-effective solution. In this study, a multiplex lateral flow immunoassay (DPP Fever Panel II Assay) that can detect serum immunoglobulin M (IgM) and specific microbial antigens of common fever agents in Asia (Orientia tsutsugamushi, Rickettsia typhi, Leptospira spp., Burkholderia pseudomallei, Dengue virus, Chikungunya virus, and Zika virus), was evaluated. METHODOLOGY/PRINCIPAL FINDINGS: Whole blood (WB) and serum samples from 300 patients with undefined febrile illness (UFI) recruited in Vientiane, Laos PDR were tested using the DPP Fever Panel II, which consists of an Antibody panel and Antigen panel. To compare reader performance, results were recorded using two DPP readers, DPP Micro Reader (Micro Reader 1) and DPP Micro Reader Next Generation (Micro Reader 2). WB and serum samples were run on the same fever panel and read on both micro readers in order to compare results. ROC analysis and equal variance analysis were performed to inform the diagnostic validity of the test compared against the respective reference standards of each fever agent (S1 Table). Overall better AUC values were observed in whole blood results. No significant difference in AUC performance was observed when comparing whole blood and serum sample testing, except for when testing for R. typhi IgM (p = 0.04), Leptospira IgM (p = 0.02), and Dengue IgG (p = 0.03). Linear regression depicted R2 values had ~70% agreement across WB and serum samples, except when testing for leptospirosis and Zika, where the R2 values were 0.37 and 0.47, respectively. No significant difference was observed between the performance of Micro Reader 1 and Micro Reader 2, except when testing for the following pathogens: Zika IgM, Zika IgG, and B pseudomallei CPS Ag. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that the diagnostic accuracy of the DPP Fever Panel II is comparable to that of commonly used RDTs. The optimal cut-off would depend on the use of the test and the desired sensitivity and specificity. Further studies are required to authenticate the use of these cut-offs in other endemic regions. This multiplex RDT offers diagnostic benefits in areas with limited access to healthcare and has the potential to improve field testing capacities. This could improve tropical fever management and reduce the public health burden in endemic low-resource areas.

From fever to action: diagnosis, treatment, and prevention of acute undifferentiated febrile illnesses.

Acute Undifferentiated Febrile Illness (AUFI) presents a clinical challenge, often characterized by sudden fever, non-specific symptoms, and potential life-threatening implications. This review highlights the global prevalence, types, challenges, and implications of AUFI, especially in tropical and subtropical regions where infectious diseases thrive. It delves into the difficulties in diagnosis, prevalence rates, regional variations, and potential causes, ranging from bacterial and viral infections to zoonotic diseases. Furthermore, it explores treatment strategies, preventive measures, and the critical role of the One Health approach in addressing AUFI. The paper also addresses the emerging zoonotic risks and ongoing outbreaks, including COVID-19, Rickettsia spp., and other novel pathogens, emphasizing their impact on AUFI diagnosis and management. Challenges in resource-limited settings are analyzed, highlighting the need for bolstered healthcare infrastructure, enhanced diagnostics, and collaborative One Health strategies. Amidst the complexity of emerging zoonotic threats, this review underscores the urgency for a multifaceted approach to mitigate the growing burden of AUFI, ensuring early diagnosis, appropriate treatment, and effective prevention strategies.

Performance of Febrile Infant Algorithms by Duration of Fever.

OBJECTIVES: To analyze the performance of commonly used blood tests in febrile infants ≤90 days of age to identify patients at low risk for invasive bacterial infection (bacterial pathogen in blood or cerebrospinal fluid) by duration of fever. METHODS: We conducted a secondary analysis of a prospective single-center registry that includes all consecutive infants ≤90 days of age with fever without a source evaluated at 1 pediatric emergency department between 2008 and 2021. We defined 3 groups based on caregiver-reported hours of fever (<2, 2-12, and ≥12) and analyzed the performance of the biomarkers and Pediatric Emergency Care Applied Research Network, American Academy of Pediatrics, and Step-by-Step clinical decision rules. RESULTS: We included 2411 infants; 76 (3.0%) were diagnosed with an invasive bacterial infection. The median duration of fever was 4 (interquartile range, 2-12) hours, with 633 (26.3%) patients with fever of <2 hours. The area under the curve was significantly lower in patients with <2 hours for absolute neutrophil count (0.562 vs 0.609 and 0.728) and C-reactive protein (0.568 vs 0.760 and 0.812), but not for procalcitonin (0.749 vs 0.780 and 0.773). Among well-appearing infants older than 21 days and negative urine dipstick with <2 hours of fever, procalcitonin ≥0.14 ng/mL showed a better sensitivity (100% with specificity 53.8%) than that of the combination of biomarkers of Step-by-Step (50.0% and 82.2%), and of the American Academy of Pediatrics and Pediatric Emergency Care Applied Research Network rules (83.3% and 58.3%), respectively. CONCLUSIONS: The performance of blood biomarkers, except for procalcitonin, in febrile young infants is lower in fever of very short duration, decreasing the accuracy of the clinical decision rules.

[Fever in rheumatological diseases]. / Fieber bei rheumatologischen Erkrankungen.

Fever is a frequent and important symptom in patients with rheumatological diseases and can be an expression of activity of the underlying rheumatological disease. There is great variability in the incidence of fever as a symptom of the disease between individual diseases. The growing understanding of the molecular signatures of the diseases can help to explain these discrepancies: A genetic overactivation of potently pyrogenic cytokines is the reason why fever is nearly always present in autoinflammatory syndromes. In contrast, fever is less common in polyarthritis and myositis and mostly limited to severe courses of disease. In the diagnostic work-up of fever, frequent differential diagnoses, such as infections, malignancies, side effects of drugs and hypersensitivity reactions should be considered. This article provides an overview of the physiology of the development of fever, describes the relevance of fever in individual rheumatological diseases and proposes a workflow for the clinical clarification of rheumatological patients who present with fever.

[Infections and fever]. / Infektion und Fieber.

Fever can be due to infectious or noninfectious causes and results from the body's natural response to exogenous or endogenous pyrogens. Laboratory tests including complete blood count, differential blood count, C­reactive protein, erythrocyte sedimentation rate and procalcitonin do not have sufficient sensitivity and specificity to definitively detect or rule out an infectious (bacterial, viral, parasitic) cause of fever. Blood cultures should be carried out when bacteremic or septic illnesses are suspected. Fever is not always present in infections and can be absent, especially in older and immunocompromised patients. If fever is suspected, core temperatures should be taken, e.g., rectally, orally or invasively. Depending on the clinical situation, infectious causes must be excluded as the most likely cause of an acutely occurring fever. The investigation of long-standing fever (fever of unknown origin, FUO) can be complex and some infectious diseases should first be ruled out, whereby a syndromic classification often helps to clarify the cause of the fever.

Addition of constitutional symptoms to the SLEDAI-2K improves overall disease activity assessment: A pilot study.

OBJECTIVE: Constitutional symptoms (fatigue, lymphadenopathy, and weight loss) are not included in the SLE disease activity index-2000 (SLEDAI-2K). In this pilot study, we assessed the concurrent and construct validity of a revised SLEDAI-2K (SLED-R) that included these symptoms with the original SLEDAI-2K (SLED-O), using the physician global assessment of disease activity (PGA) as the reference. METHODS: Our revised SLED-R substituted the SLED-O's fever descriptor with a constitutional descriptor that included fever, fatigue, lymphadenopathy, and/or weight loss. SLED-O, SLED-R, PGA and patient global assessment (PtGA) scores were collected prospectively. Bland-Altman correlations for repeated measures were calculated and Meng's z-test was used to compare correlations between dependent and overlapping correlation coefficients. Associations between constitutional symptoms and disease activity measures were analyzed using Mann-Whitney U, Kruskal-Wallis, Chi-square tests and repeated measures correlations. RESULTS: 1123 SLED-O, SLED-R, PGA, and 1066 PtGA were collected in 239 subjects. The new descriptor was scored in 45 subjects (18.8%) and 92 instances (8.1%), while the original descriptor, fever, was scored in only 4 subjects (1.7%) and 5 instances (0.4%). Mean SLED-O, PGA and PtGA scores were higher when the constitutional descriptor was scored versus not (p < .001). The correlation between SLED-R and PGA was marginally higher than between SLED-O and PGA (p < .001). Fatigue contributed most to this increase (p = .001) and associated with both higher PGA and PtGA scores (p < .001). Mean SLED-O and PGA scores were higher when ≥1 constitutional symptom(s) were scored versus not (p < .002). Correlations between PGA and PtGA when the new descriptor was scored versus not were similar (p = .860). The frequency of concordance between PGA and PtGA was lower when the new descriptor was scored (55%) versus not (72.5%), with PGA > PtGA when the new descriptor was scored (p < .001). CONCLUSION: The addition of constitutional symptoms to SLEDAI-2K, particularly fatigue, resulted in a marginal increase in its correlation with PGA, and new constitutional symptoms associated with higher SLED-O and PGA scores. As fatigue is subjective and difficult to attribute to SLE, its validity and inter-rater reliability in scoring remains uncertain. The clinical utility of SLED-R remains unclear, and further studies of its validity and reliability are needed.