Plasma Profiling of Acute Myeloid Leukemia With Fever- and Infection-Related Complications During Chemotherapy-Induced Neutropenia.

BACKGROUND: Acute myeloid leukemia (AML) is a heterogenous and complex blood cancer requiring aggressive treatment. Early identification and prediction of the complications following treatment is vital for effective disease management. AIMS: We explored associations between plasma protein levels and fever- and infection-related complications in 26 AML patients during chemotherapy-induced neutropenia. MATERIAL AND METHODS: Longitudinal plasma profiling was conducted using data-dependent mass spectrometry analysis. RESULTS: Mass spectrometry-based plasma profiling data correlated well with laboratory parameters, including C-reactive protein, and revealed a broader inflammation protein network associated with fever- and infection-related complications. DISCUSSION AND CONCLUSION: These data indicate the potential of longitudinal plasma profiling in AML patients for identifying and predicting complications that may aid in improved disease monitoring and treatment.

Seropositivity of West Nile virus among acute febrile patients in Ilorin, Nigeria.

INTRODUCTION: West Nile Virus (WNV), a member of Flaviviridae family, is one of the most widely distributed arboviruses in the world. In developing countries like Nigeria, fever resulting from the WNV infection is often presumptively ascribed to malaria or typhoid due to misdiagnosis and low-level awareness of the viral infection. This study determined the prevalence of WNV IgM and IgG antibodies among febrile patients in the Ilorin metropolis. MATERIALS AND METHODS: A total of two hundred (200) blood samples were collected from consenting patients and each serum was screened for anti-WNV IgM and IgG antibodies using indirect enzyme-linked immunosorbent assay (ELISA). Statistical correlation and logistic regression analysis were conducted. RESULTS: Overall, 6% (12/200) anti-WNV IgM seropositivity rate was recorded amongst the acute febrile patients with higher prevalence (6.30%) in females than in males (5.45%). Anti-WNV IgG positivity rate of 52% (104/200) was recorded, with 50.67% positivity rate in males and 38.95% in female participants. The convalescence phase posited by the 5.4% (11/200) co-detection of anti-WNV IgG and IgM antibodies among the participants was recorded. A statistical correlation was noticed with the age and religion of respondents to WNV serological positivity while gender, occupation, use of mosquito nets and formal education had no positive correlation at p < 0.05. However, based on odd ratio at 95% CI and logistic regression coefficients, the evaluated risk factors such as blood transfusion, residency, malaria parasite, and proximity to stagnant water and bush were significant to anti-WNV IgG and IgM positivity. CONCLUSION: The findings of this study show the circulation of WNV in the study area. There is an urgent need for clinicians/physicians to include screening for the West Nile virus in cases of febrile patients before the commencement of treatment.

Association between neutrophil-to-lymphocyte ratio and epidural-related maternal fever in Chinese parturients: a prospective cohort study.

OBJECTIVE: Epidural analgesia could increase the risk of maternal fever during labor, and the potential mechanisms involved inflammation. Neutrophil-to-lymphocyte ratio (NLR) was a sensitive inflammatory composite indicator and related to adverse outcomes in parturients. This study aimed to investigate the association between NLR levels and epidural related maternal fever (ERMF). METHODS: This prospective cohort study included 614 parturients who underwent epidural analgesia at the Women's Hospital School of Medicine Zhejiang University from November 2021 to May 2023. NLR level was calculated before epidural analgesia for women. The outcome was ERMF. Univariate and multivariate logistic regression models were utilized to explore the association between NLR level and ERMF. And the association was further investigated in subgroups of age, body mass index (BMI) before pregnancy, and parity of delivery. The results were presented as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Totally, 614 parturients, of whom 171 (27.85%) had ERMF. High NLR level was associated with higher incidence of ERMF (OR = 2.70, 95% CI: 1.58-4.69). Parturients with ERMF had higher proportion of postpartum hemorrhage, longer labor times, and other adverse outcomes in parturients. The association also observed in subgroups of age <35 years old (OR = 2.74, 95% CI: 1.55-4.29), BMI <24 kg/m2 before pregnancy (OR = 2.32, 95% CI: 1.32-4.13), BMI ≥24 kg/m2 before pregnancy (OR = 38.28, 95%CI: 3.67-854.66), primipara (OR = 2.26, 95% CI:1.27-4.04), and multipara (OR = 30.60, 95% CI: 3.73-734.03). CONCLUSION: High NLR levels were associated with ERMF in women. It indicated that physicians may measure NLR levels as a regular measurement, which may beneficial for pregnancy outcomes.

Diagnostic Accuracy of Serum Procalcitonin to Diagnose Sepsis in Advanced Solid Tumor Patients with Fever.

BACKGROUND: Diagnosis of infection in advanced solid tumor patients can be challenging since signs and symptoms might be overlapping due to paraneoplastic condition. Delay diagnosis of existing infection can lead to more severe conditions and increased mortality. Procalcitonin (PCT) has been used to support the diagnosis of bacterial infection and sepsis. Unfortunately, PCT also increases in malignancy even without an infection. We investigated the diagnostic accuracy of PCT in advanced solid tumor patients with fever to diagnose sepsis. METHODS: A cross-sectional study was conducted in solid advanced tumor patients with fever patients who were admitted to Cipto Mangunkusumo Hospitals, Indonesia between June 2016 and April 2018. Sepsis was defined using 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference criteria. The diagnostic accuracy of PCT was determined using the receiver operating characteristic (ROC) curve. RESULTS: A total of 194 subjects were enrolled in this study. 60.3% were female with a mean age of 49.47±12.87 years old. 143 patients (73.7%) with advanced solid tumors. Among this latter group, 39 patients (27%) were sepsis. The ROC curve showed that the levels of PCT for sepsis in advanced solid tumor patients with fever were in the area under the curve (AUC) 0.853 (95%CI 0.785 - 0.921). The Cut-off of PCT in advanced solid tumor patients with fever to classify as sepsis was 2.87 ng/mL, with a sensitivity of 79.5%, and a specificity of 79.8%. CONCLUSION: PCT has good diagnosis accuracy in advanced solid tumor patients with fever to classify as sepsis, however a higher cut-off compared to non-cancerous patients should be used.

Role of mitochondrial DNA level in epidural-related maternal fever: a single-centre, observational, pilot study.

INTRODUCTION: Epidural analgesia has been associated with intrapartum maternal fever development. Epidural-related maternal fever (ERMF) is believed to be based on a non-infectious inflammatory reaction. Circulating cell-free mitochondrial deoxyribonucleic acid (mtDNA) is one of the possible triggers of sterile inflammatory processes; however, a connection has not been investigated so far. Therefore, this study aimed to investigate cell-free mtDNA alterations in women in labour with ERMF in comparison with non-febrile women. MATERIAL AND METHODS: A total of 60 women in labour were assessed for maternal temperature every 4 h and blood samples were obtained at the beginning and after delivery. Depending on the analgesia and the development of fever (axillary temperature ≥ 37.5 °C), the women were allocated either to the group of no epidural analgesia (n = 17), to epidural analgesia no fever (n = 34) or to ERMF (n = 9). Circulating cell-free mtDNA was analysed in the maternal plasma for the primary outcome whereas secondary outcomes include the evaluation of inflammatory cytokine release, as well as placental inflammatory signs. RESULTS: Of the women with epidural analgesia, 20% (n = 9) developed ERMF and demonstrated a decrease of circulating mtDNA levels during labour (p = 0.04), but a trend towards higher free nuclear DNA. Furthermore, women with maternal pyrexia showed a 1.5 fold increased level of Interleukin-6 during labour. A correlation was found between premature rupture of membranes and ERMF. CONCLUSIONS: The pilot trial revealed an evident obstetric anaesthesia phenomenon of maternal fever due to epidural analgesia in 20% of women in labour, demonstrating counterregulated free mtDNA and nDNA. Further work is urgently required to understand the connections between the ERMF occurrence and circulating cell-free mtDNA as a potential source of sterile inflammation. TRIAL REGISTRATION: NCT0405223 on clinicaltrials.gov (registered on 25/07/2019).

[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.

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.

Characterizing the blood microbiota in healthy and febrile domestic cats via 16s rRNA sequencing.

This study aimed to evaluate the blood bacterial microbiota in healthy and febrile cats. High-quality sequencing reads from the 16S rRNA gene variable region V3-V4 were obtained from genomic blood DNA belonging to 145 healthy cats, and 140 febrile cats. Comparisons between the blood microbiota of healthy and febrile cats revealed dominant presence of Actinobacteria, followed by Firmicutes and Proteobacteria, and a lower relative abundance of Bacteroidetes. Upon lower taxonomic levels, the bacterial composition was significantly different between healthy and febrile cats. The families Faecalibacterium and Kineothrix (Firmicutes), and Phyllobacterium (Proteobacteria) experienced increased abundance in febrile samples. Whereas Thioprofundum (Proteobacteria) demonstrated a significant decrease in abundance in febrile. The bacterial composition and beta diversity within febrile cats was different according to the affected body system (Oral/GI, systemic, skin, and respiratory) at both family and genus levels. Sex and age were not significant factors affecting the blood microbiota of febrile cats nor healthy ones. Age was different between young adult and mature adult healthy cats. Alpha diversity was unaffected by any factors. Overall, the findings suggest that age, health status and nature of disease are significant factors affecting blood microbiota diversity and composition in cats, but sex is not.

Role of inflammatory markers in the assessment of meningitis in adult patients with fever and headache.

BACKGROUND: Meningitis, especially of bacterial origin, is a medical emergency that must be diagnosed promptly. However, due to the associated risks of complications of lumbar puncture, it is crucial to identify individuals who truly need it. The aim of this study was to assess the diagnostic role of inflammatory markers in distinguishing among patients without meningitis, those with aseptic meningitis, and those with bacterial meningitis. METHODS: This was a retrospective, diagnostic study at an acute care hospital, involving adult patients who presented to either ambulatory care or the emergency department with fever and headache, but without altered mental status or neurological deficits. Inflammatory markers (C-reactive protein [CRP], mean platelet volume, neutrophil-lymphocyte ratio, and red cell distribution width) were assessed as index tests. An expert panel classified patients into three groups: no meningitis, aseptic meningitis, and bacterial meningitis using predefined criteria. RESULTS: Of the 80 patients, 52 had no meningitis, 27 had aseptic meningitis, and 1 had bacterial meningitis. Of the inflammatory markers investigated, only CRP showed potential usefulness in differentiating these three diagnostic groups, with median values of 5.6 (interquartile range [IQR] 2.1, 11.3) mg/dL in those without meningitis, 0.2 (IQR 0.1, 1.2) mg/dL in those with aseptic meningitis, and notably elevated at 21.7 mg/dL in the patient with bacterial meningitis. CONCLUSION: In adult patients presenting with fever and headache in an emergency setting, CRP was the only marker that demonstrated potential diagnostic utility in distinguishing among those with no meningitis, aseptic meningitis, and bacterial meningitis.

Complete Pathologic Response to Neoadjuvant Chemoimmunotherapy and Oxaliplatin-Induced Fever Associated With IL-6 Release in a Patient With Locally Advanced Colon Cancer

Neoadjuvant systemic therapy is a preferred treatment approach for a number of tumor types due to many potential advantages over upfront surgery, including tumor downstaging, early treatment of micrometastatic disease, and providing an in vivo test of tumor biology. For colon cancer, current standard of care is upfront surgery followed by adjuvant systemic therapy in high-risk patients. Concerns about inaccurate radiological staging and tumor progression during preoperative treatment, as well the lack of randomized data demonstrating benefit, are among the reasons for the limited use of neoadjuvant therapy in this disease. Locally advanced colon cancer, defined as primary colon cancer with direct invasion into the adjacent structures or extensive regional lymph node involvement, is not always amenable to pathological complete resection, and when attempted it comes with high incidence of postoperative morbidity and mortality because of the required multivisceral resection. Clinical trials of neoadjuvant chemotherapy for colon cancer to date have been promising with downstaging of disease and higher rates of R0 resection. Here, we report a case of a patient with locally advanced, unresectable, mismatch repair deficient sigmoid colon cancer who was treated with neoadjuvant chemoimmunotherapy followed by surgical resection leading to a complete pathologic response after preoperative systemic chemoimmunotherapy.

Immunoglobulin signature predicts risk of post-acute COVID-19 syndrome.

Following acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a significant proportion of individuals develop prolonged symptoms, a serious condition termed post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) or long COVID. Predictors of PACS are needed. In a prospective multicentric cohort study of 215 individuals, we study COVID-19 patients during primary infection and up to one year later, compared to healthy subjects. We discover an immunoglobulin (Ig) signature, based on total IgM and IgG3 levels, which - combined with age, history of asthma bronchiale, and five symptoms during primary infection - is able to predict the risk of PACS independently of timepoint of blood sampling. We validate the score in an independent cohort of 395 individuals with COVID-19. Our results highlight the benefit of measuring Igs for the early identification of patients at high risk for PACS, which facilitates the study of targeted treatment and pathomechanisms of PACS.

Growth and differentiation factor-15 as a potential prognostic biomarker for status-epilepticus-associated-with-fever: A pilot study.

OBJECTIVE: Biomarkers predicting poor outcomes of status-epilepticus-associated-with-fever (SEF) at an early stage may contribute to treatment guidance. However, none have been reported thus far. We investigated the dynamics of serum growth and differentiation factor (GDF)-15 after seizure onset in patients with SEF and determined whether GDF-15 can predict poor outcomes, particularly in the first 6 h after seizure onset. METHODS: We enrolled 37 pediatric patients with SEF and eight patients with simple febrile seizures (SFS) and collected their blood samples within 24 h of seizure onset and eight febrile control patients between March 1, 2017 and September 30, 2020. All patients were aged ≤15 years. RESULTS: In the SEF group, the median post-seizure serum GDF-15 values were 1,065 (<6h), 2,720 (6-12 h), and 2,411 (12-24 h) pg/mL. The median serum GDF-15 in the first 6 h was measured in patients with SEF without a significant past medical history (n = 21) and was found to be statistically significantly higher (1,587 pg/mL) than in the febrile control (551 pg/mL) and SFS (411 pg/mL) groups. The median serum GDF-15 was statistically significantly higher in patients with SEF with sequelae (n = 5) and patients with acute encephalopathy with biphasic seizures/reduced diffusion/hemorrhagic shock and encephalopathy syndrome (n = 6) than in patients with SEF without sequelae (n = 16) (15,898 vs 756 pg/mL) and patients with prolonged FS (n = 15) (9,448 vs 796 pg/mL). CONCLUSIONS: This study demonstrates the dynamics of serum GDF-15 in patients with SEF and indicates the potential of GDF-15 as an early predictor of poor outcomes.

Impact of Paired Central and Peripheral Blood Cultures in Children With Cancer.

Children with cancer require central venous access which carries risk for line-related infections. The necessity of peripheral and central blood cultures is debated for those with fevers. We evaluated and described results for first episode of paired blood cultures from children with cancer who have a central venous line using retrospective database. Blood culture results, laboratory data, and medical outcomes were included. Descriptive analyses of blood culture results and clinical data were performed. There were 190 episodes of paired positive blood cultures with 167 true positive episodes. Of the true positive episodes, 104 (62.3%) were positive in both central and peripheral cultures, 42 (25.1%) were positive in central only cultures, and 21 (12.6%) were positive in peripheral cultures only. Intensive care unit admission within 48 hours after blood cultures (n=33) differed significantly: 28.7% for both central and peripheral, 10% for central only, and 0% for peripheral only (P=0.009). Central line removal (n=34) differed by type of positivity but was not significant: 22.1% for both central and peripheral, 23.8% for central only, and 4.8% for peripheral only (P=0.15). Peripheral blood cultures provided important medical information yet had differences in short-term clinical outcomes. Further evaluation of medical decision making is warranted.

Bacteremia in Febrile, Non-neutropenic, and Well-appearing Children With Cancer.

Fever in a neutropenic pediatric oncology patient requires prompt assessment due to the risk of infectious complications. The appropriate management of fever in non-neutropenic patients, however, is not well-established. We describe the rate of bacteremia in a cohort of non-neutropenic pediatric oncology patients with fever at a large institution. Patients were included if they presented to the emergency department or outpatient clinic between 2009 and 2014 with fever, had a central venous catheter (CVC), and were not neutropenic. Three hundred eighty-six episodes of fever occurring in 159 patients were included in the data analysis. Fifty-nine percent of patients were male, 41% had a diagnosis of acute lymphoblastic leukemia, and 90% had a port-a-cath as CVC. The rate of bacteremia was 3.4%; presence of a port-a-cath was protective against bacteremia whereas a white blood cell count >20,000/mm3 was associated with a higher likelihood of bacteremia. Gram-positive microorganisms were most commonly isolated (64.3%) and frequently resistant to cephalosporins. In summary, in our study, the rate of bacteremia was low among non-neutropenic, well-appearing pediatric cancer patients with a CVC and was not associated with any serious medical complications. Prospective research is needed to determine the most appropriate management of these patients.

Evaluation of risk factors associated with first episode febrile seizure.

OBJECTIVE: Febrile convulsion (FC) is one of the most common neurological findings in children. This study was aimed to investigate the difference in laboratory parameters between Febrile Seizure and control groups. PATIENTS AND METHODS: In this study, 169 children admitted to the pediatric emergency department with their first episode of FS and 189 control groups were retrospectively analyzed. The demographic characteristics and laboratory parameters of children were obtained from their files. RESULTS: Upper respiratory tract infection (URTI) was determined the most common disease (81.6%) in the FC group followed by acute gastroenteritis (AGE) (15.4%) and urinary tract infection (UTI) (3%), respectively. Similarly, URTI was detected as the most common disease (81.8%) in control groups. It was determined that there was no statistically significant difference between the two groups in terms of diseases. The leukocyte and neutrophil counts of the children with FC were significantly higher but the mean corpuscular volume of lenfosit and lenfosit/neutrophil ratio was significantly lower than the control groups (p= 0.009, <0.001, 0.001, <0.001, <0.001, respectively). Children with FC had significantly higher blood glucose, urea, creatinine, creatine kinase, alkaline phosphatase and albumin levels compared with the control groups (p<0.001, in all parameters). On the other hand, the potassium, sodium and chlorine levels of the Children with FCs were significantly lower than control groups (p=0.017, <0.001, p <0.001, respectively). CONCLUSIONS: To conclude, febrile patients with high leukocyte counts, high neutrophil counts, and several biochemical parameters should be carefully monitored for FCs due to the increasing seizure risk.

Cost-effectiveness of point-of-care C-Reactive Protein test compared to current clinical practice as an intervention to improve antibiotic prescription in malaria-negative patients in Afghanistan.

BACKGROUND: Antimicrobial resistance (AMR) is a global health problem requiring a reduction in inappropriate antibiotic prescribing. Point-of-Care C-Reactive Protein (POCCRP) tests could distinguish between bacterial and non-bacterial causes of fever in malaria-negative patients and thus reduce inappropriate antibiotic prescribing. However, the cost-effectiveness of POCCRP testing is unclear in low-income settings. METHODS: A decision tree model was used to estimate cost-effectiveness of POCCRP versus current clinical practice at primary healthcare facilities in Afghanistan. Data were analysed from healthcare delivery and societal perspectives. Costs were reported in 2019 USD. Effectiveness was measured as correctly treated febrile malaria-negative patient. Cost, effectiveness and diagnostic accuracy parameters were obtained from primary data from a cost-effectiveness study on malaria rapid diagnostic tests in Afghanistan and supplemented with POCCRP-specific data sourced from the literature. Incremental cost-effectiveness ratios (ICERs) reported the additional cost per additional correctly treated febrile malaria-negative patient over a 28-day time horizon. Univariate and probabilistic sensitivity analyses examined the impact of uncertainty of parameter inputs. Scenario analysis included economic cost of AMR per antibiotic prescription. RESULTS: The model predicts that POCCRP intervention would result in 137 fewer antibiotic prescriptions (6%) with a 12% reduction (279 prescriptions) in inappropriate prescriptions compared to current clinical practice. ICERs were $14.33 (healthcare delivery), $11.40 (societal), and $9.78 (scenario analysis) per additional correctly treated case. CONCLUSIONS: POCCRP tests could improve antibiotic prescribing among malaria-negative patients in Afghanistan. Cost-effectiveness depends in part on willingness to pay for reductions in inappropriate antibiotic prescribing that will only have modest impact on immediate clinical outcomes but may have long-term benefits in reducing overuse of antibiotics. A reduction in the overuse of antibiotics is needed and POCCRP tests may add to other interventions in achieving this aim. Assessment of willingness to pay among policy makers and donors and undertaking operational trials will help determine cost-effectiveness and assist decision making.

A novel nairovirus associated with acute febrile illness in Hokkaido, Japan.

The increasing burden of tick-borne orthonairovirus infections, such as Crimean-Congo hemorrhagic fever, is becoming a global concern for public health. In the present study, we identify a novel orthonairovirus, designated Yezo virus (YEZV), from two patients showing acute febrile illness with thrombocytopenia and leukopenia after tick bite in Hokkaido, Japan, in 2019 and 2020, respectively. YEZV is phylogenetically grouped with Sulina virus detected in Ixodes ricinus ticks in Romania. YEZV infection has been confirmed in seven patients from 2014-2020, four of whom were co-infected with Borrelia spp. Antibodies to YEZV are found in wild deer and raccoons, and YEZV RNAs have been detected in ticks from Hokkaido. In this work, we demonstrate that YEZV is highly likely to be the causative pathogen of febrile illness, representing the first report of an endemic infection associated with an orthonairovirus potentially transmitted by ticks in Japan.

Evidence of chikungunya virus infections among febrile patients at three secondary health facilities in the Ashanti and the Bono Regions of Ghana.

BACKGROUND: Chikungunya is now of public health concern globally due to its re-emergence in endemic areas and introduction into new areas of the world. Worldwide, the vectors for transmission of the chikungunya virus are Aedes mosquitoes and these are prevalent in Ghana. Despite its global significance, the true burden of chikungunya virus infection in Ghana is largely unknown and the threat of outbreak remains high owing to international travel. This study sought to determine chikungunya virus infection among febrile patients suspected of having malaria infections at some selected health facilities in the Ashanti, Bono East, and Bono Regions of Ghana. METHODOLOGY: This cross-sectional study recruited six hundred (600) febrile patients suspected of having malaria who submitted their clinical samples to the laboratories of the selected health facilities for the diagnosis of their infections. Five to ten millilitres (5-10ml) of venous blood were collected from each study participant. Sera were separated and tested for anti-chikungunya (IgM and IgG) antibodies using InBios ELISA kit following the manufacturer's instruction. Samples positive for chikungunya IgM and IgG were selected and tested for chikungunya virus RNA using Reverse Transcription-quantitative Polymerase Chain Reaction. Malaria Rapid Diagnostic Test kits were used to screen the participants for malaria. Structured questionnaires were administered to obtain demographic and clinical information of the study participants. RESULT: Of the 600 samples tested, the overall seroprevalence of chikungunya was 6%. The seroprevalence of chikungunya IgM and IgG antibodies were 1.8% and 4.2% respectively. None of the chikungunya IgM and IgG positive samples tested positive for chikungunya RNA by RT-qPCR. Of the 600 samples, tested 32.3% (194/600) were positive for malaria parasites. Malaria and chikungunya co-infection was detected in 1.8% (11/600) of the participants. CONCLUSION: Findings from the current study indicate low-level exposure to the chikungunya virus suggesting the virus is circulating and potentially causing morbidity in Ghana.

Prolonged Fever: An Atypical Presentation in MOG Antibody-Associated Disorders.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelinating disorders (MOGAD) are increasingly being recognized in the pediatric age group. Over time, unusual presentations have expanded the clinical presentation. We report 12 cases of MOGAD where prolonged fever (PF) was an important part of the symptom complex during the course of the illness. METHODS: After initial recognition of this atypical clinical presentation, more patients were recruited over 2 years and followed up prospectively. RESULTS: Eight of twelve patients had no clinical/imaging evidence of demyelination until much later in the course. Three clinical presentations recognized were fever of unknown origin (4 of 12), aseptic meningitis (4 of 12), and PF seen concurrently with established acute demyelination syndrome (4 of 12). Leukocytosis, raised inflammatory markers, and cerebrospinal fluid pleocytosis were almost universal. The first two presentations frequently caused diagnostic confusion, as MOGAD was not considered until several weeks after disease onset. The third group was more a therapeutic conundrum on how to manage the PF. Early seizures without encephalopathy were not uncommon and were probably independent of the later-appearing demyelination. CONCLUSIONS: This case series highlights PF as an important component of the pediatric MOGAD symptom complex. MOGAD could be considered in the differential diagnosis of these clinical presentations.