Febrile Controls Research Articles

Tight junction protein ZO-1 in Kawasaki disease

BackgroundKawasaki disease (KD) is a form of systemic febrile vasculitis that is complicated with coronary artery lesions (CAL). The tight junctions that maintain the intestinal barrier also play a role in systemic inflammatory diseases. Serum zonula occludens-1 (ZO-1) expression was found to be significantly lower in asthmatic patients, and another study reported that elevated systemic ZO-1 was positively correlated with inflammation in cirrhotic patients. A murine model of KD vasculitis demonstrated that vasculitis depended on intestinal barrier dysfunction, which is maintained by tight junctions. In this study, we aimed to investigate the role of the tight junction zonula occludens-1 (ZO-1) in the treatment response of intravenous immunoglobulin (IVIG) and the occurrence of CAL formation in KD patients.MethodsWe enrolled 40 KD patients, 12 healthy controls, and 12 febrile controls in this study. The serum levels of tight junction ZO-1 were determined by enzyme-linked immunosorbent assay.ResultsThe serum ZO-1 level was higher in the fever control group but did not reach a statistical significance. KD patients who received a second dose of IVIG treatment due to initial IVIG unresponsiveness had a higher serum levels of tight junction ZO-1, but without statistical significance (2.15 ± 0.18 vs. 2.69 ± 0.31 ng/mL, p = 0.058). KD patients who developed a CAL demonstrated a significant lower serum tight junction ZO-1 levels than KD without CAL formation (1.89 ± 0.16 vs. 2.39 ± 0.15 ng/mL, p = 0.027). After multiple logistic regression analysis, ZO-1 levels [(95% confidence interval (CI): 0.058 ~ 0.941, odds ratio (OR) = 0.235, p = 0.041)] showed as the risk factor for CAL formation.ConclusionSerum levels of tight junction ZO-1 levels were lower in KD patients than fever controls and associated with CAL formation.

Monocyte platelet aggregates in children with Kawasaki disease- a preliminary study from a tertiary care centre in North-West India

BackgroundPlatelet activation is an integral part of pathogenesis of Kawasaki disease (KD). However, there is paucity of literature on flow-cytometry based assessment of platelet activation in KD. We aimed to analyse monocyte-platelet aggregates (MPAs), one of the sensitive markers for platelet activation, by flow cytometry in children with KD.FindingsIn this single-centre prospective study, we have enrolled 14 children with KD and results were compared with age-matched febrile (n = 15) and healthy (n = 13) controls. After gating monocytes in side-scatter plot, MPAs were identified based on CD14 and CD41 expression. Two (2) ml of blood samples for children with KD were collected at 3 phases of illness- acute stage before start of intravenous immunoglobulin or aspirin, 24 h after completion of IVIg infusion, and 3 months after acute episode of KD.Children with KD had a significantly higher MPA% values [Median (IQR)- 41.3% (26.6, 52.7)] when compared with febrile [Median (IQR)- 5.98% (2.98-9.72)] and normal [Median (IQR)- 4.48% (2.57-5.59)] controls, p<0.01. On follow-up, the MPA% showed a gradual decline in children with KD, but even at 3 months, the value [Median (IQR)- 7.55% (4.15-14.6)] was higher compared to healthy controls [Median (IQR)- 4.48% (2.57-5.59)].ConclusionsOur results suggest that MPA% was significantly elevated in acute stages in children with KD and activated platelets may continue to persist even after systemic inflammation has subsided. Future studies are warranted whether objective evidence of platelet activation may guide the use of immunomodulatory and anti-platelet therapy in KD.

Biomarkers of disease severity in vivax malaria.

Severe complications have been observed and established for Plasmodium falciparum as well as P. vivax infections worldwide. Although P. vivax infection is not fully acknowledged as malignant malaria, recently life-threatening complications have been reported to occur in many studies. The recognition of biomarkers with excellent sensitivity and reliability plays a prime role in disease management. Acute inflammatory response and oxidative stress are observed in malaria due to the production of reactive oxygen species. Lipid and protein oxidative injuries are prospective biomarkers for disease severity owing to the damage caused by the parasite. We have tried to find out whether protein carbonylation (PC), lipid peroxidation (LPO) and superoxide dismutase (SOD) could suffice as a biomarker for severe vivax malaria or not. Blood samples were collected from the individuals attending Jawaharlal Nehru Medical College of Aligarh Muslim University during the wet season of malaria transmission. Microscopy and rapid diagnostic kits were used as a tool for malaria diagnosis. A total of 214 subjects were enrolled for the study: 30 febrile controls and 184 subjects with vivax malaria. Protein carbonylation and lipid peroxidation were found to be directly associated with parasite count and total antioxidant status (TAS). Increase in oxidative stress was also observed in severe vivax malaria patients. Levels of uric acid and bilirubin too were raised in complicated cases. Protein carbonylation was found to be a more reliable indicator of vivax malaria severity than lipid peroxidation.

Comparision of Iron Status Among Childrens with Simple Febrile Seizure and Control – A Hospital Based Observational Study in Eastern India

Comparision of Iron Status Among Childrens with Simple Febrile Seizure and Control – A Hospital Based Observational Study in Eastern India

Expression of MicroRNA 146a, 155, 181 and 223 in febrile seizure.

We studied microRNAs (miRNAs) -146a, -155, -181 and -223 expressions and proinflammatory cytokine levels in children with Febrile seizure (FS) and compared to febrile controls. This prospective multicenter study examined representative populations in eight different cities in Turkey between June 30, 2018 and July 1, 2019. Blood samples were taken from all children at presentation. The real time (RT) polymerase chain reaction (PCR) were used to measure the expressions of microRNAs and tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) levels were studied by enzyme-linked immuno-sorbent assay. The study was conducted with 60 children; 30 children with FS and 30 children in the febrile control group. The seizure was classified as simple FS in 73.3 % and half of the children were experiencing their first FS episode. Although the expression levels of miRNAs-146a, -181a and -155 were higher in febrile seizure patients, only miRNAs 146a level was significantly higher in FS patients. Serum TNF-α, IL-1β, IL-6 levels were higher in the FS group than the controls. The results of statistical analysis showed that there were correlations within miRNA expressions in children with FS. No differences were found considering miRNA expression between FS type, number of FS experienced. miRNAs-146a, -181a, -155 and -223 may be involved in FS pathogenesis. Altered miRNA expression levels might be an adaptive response to inflammation. New therapeutic approaches might be developed based on miRNA expressions in children with FS.

Diarrhea in Children with Plasmodium falciparum Malaria: A Case-Control Study on the Prevalence and Response to Antimalarial Treatment.

The role of Plasmodium in the etiology of acute diarrhea in developing countries remains controversial, and gastrointestinal (GI) symptoms are inconsistently reported in malaria. In this observational case-control study, we investigated the prevalence and risk factors for GI symptoms in hospitalized malarious children aged 1 month to 5 years in northern Uganda. Children with a diagnosis of Plasmodium falciparum malaria were enrolled as cases, and feverish children in whom malaria was excluded were enrolled as controls. Among 451 malarious children, 46.1% had GI symptoms at admission. Compared with controls, the frequency of diarrhea (24.8% versus 11.2%, P < 0.001) and vomiting (35.5% versus 17.5%, P < 0.001) was significantly higher in children with malaria, who had a higher chance of showing either vomiting (odds ratio [OR]: 3.22; 95% CI: 2.14-4.91) or diarrhea (OR: 3.14; 95% CI: 1.99-5.07) at hospital admission. A subgroup analysis performed in children with severe malaria, severe anemia, or high-grade fever confirmed these results. Diarrhea was more frequent in infants and children younger than 3 years than in older children. The analysis of 71 malarious children with diarrhea who received intravenous artesunate showed that the symptom resolved within the first 24 hours since the beginning of the treatment in 85.9% of cases. The 3-fold higher prevalence of diarrhea and vomiting in malarious children compared with febrile controls may provide rationale for incorporating malaria testing in the symptom-guided diagnostic approach of the young child with diarrhea and vomiting in malaria-endemic settings.

Changes of HMGB-1 and sTLR4 levels in cerebrospinal fluid of patients with febrile seizures

PurposeFever-induced inflammatory processes and pro-inflammatory cytokines have gained importance in recent years in the pathogenesis of febrile convulsion. Increased levels of HMGB1 (high mobility group box 1), one of the most important pro-inflammatory cytokines, are associated with prolongation of seizure duration, recurrence of seizures and the development of epilepsy. Changes in the sTLR4 level (soluble toll-like receptor 4) in the cerebrospinal fluid (CSF) are thought to be associated with memory and learning functions. In our study, we aimed to evaluate changes in HMGB1 and sTLR4 levels in patients who had febrile seizures between 6 months and 6 years. MethodsForty patients who were admitted to Akdeniz University Medical Faculty Hospital between April 2016 and April 2018 with a complaint of febrile seizure and 45 patients whose CSF samples were taken for complaints other than febrile convulsion (control group) were included in our study. ResultsComparison of the CSF HMGB1 levels of the febrile convulsion group and control group revealed a statistically significant increase in patients with febrile convulsions (p: 0.001). Comparison of the subgroups revealed that the mean value of CSF HMGB1 level was highest in the complex FS group with a mean value of 3363.9 ± 835,47 pg/mL. Comparison of the patient and control groups revealed that the changes in CSF sTLR4 levels were not statistically significant. ConclusionHMGB1 level, a key inflammatory molecule, was significantly higher in the CSF of children with febrile seizures. Our data suggest that the HMGB1 network may contribute to the generation of febrile seizures in children.

Iron deficiency in febrile seizures: a prospective case control study

Background: The objective of the study was to evaluate the role of iron deficiency in febrile seizures.Methods: Case control study conducted at Pediatric department of Tertiary care hospital. A total 70 cases and 70 controls were included in the study. Consecutive cases and controls were selected. Cases were children of age group 6 months to 5 years with simple febrile seizures and controls were children of same age group with short febrile illness without any seizures. After consent, detailed history was taken and clinical examination were carried out for both groups. Blood investigations were done to diagnose iron deficiency in both cases and controls. Iron deficiency was diagnosed as per WHO criteria haemoglobin &lt;11 g/dl in cases &lt;5 years mean corpuscular volume&lt;70 fl, mean corpuscular haemoglobin &lt;27 pg and serum ferritin&lt;30 microgram/dl.Results: Mean corpuscular volume was less than 70 fl/ml in 51% cases and 31% controls and mean corpuscular hemoglobin was less than 27 pg/ml in 84% cases and 40% of controls indicating statistically significant association of MCV and MCH between cases and controls .Serum ferritin was less than 30 ng/ml in 44% in cases as compared to 26% of controls, there was statistically significant difference between serum ferritin levels in cases and controls. From the above findings, study showed statistically significant association between iron deficiency anaemia and febrile seizures (p value &lt;0.01; OR- 8.05 (3.6-17.93) (df-1).Conclusions: Iron deficiency is a major risk factor for simple febrile seizures in age group of 6 months to 60 months.

Association between iron deficiency anaemia and simple febrile seizure in South Indian rural population

Background: Simple febrile seizure is a common problem worldwide, many studies have investigated the etiology and natural history of febrile seizures and evaluated various management strategies, but very little information is available about iron deficiency as a risk factor. Hence, we aimed to determine the association between iron deficiency anaemia and simple febrile seizures in south Indian rural population. Methods: It is an observational study done in paediatrics department at Sri Venkateshwaraa medical college hospital and research centre. A total 120 (60 cases and 60 control) were included in the study. Children with febrile seizures and controls were included fever without seizures. Informed consent was taken from parents of each child. Children were divided into two groups, cases and controls. Serum ferritin level, Hb, HCT and MCV levels were assessed.Results: Mean Hb level in cases and controls were 9.1±1.2 and 12.7±1.7 mg/dl respectively. Mean MCV value in cases and controls was 78.1±6.2 and 81.4±6.9 respectively. Mean serum iron level in cases was 29.9±4.9 and in controls mean serum iron level was 42.8±7.4. Conclusions: Iron deficiency anaemia is considered as a risk factor for febrile seizures in children.

A New Diagnostic Model to Distinguish Kawasaki Disease From Other Febrile Illnesses in Chongqing: A Retrospective Study on 10,367 Patients.

Objective: Kawasaki disease (KD) is one of the most prevailing vasculitis among infants and young children, and has become the leading cause of acquired heart disease in childhood. Delayed diagnosis of KD can lead to serious cardiovascular complications. We sought to create a diagnostic model to help distinguish children with KD from children with other febrile illnesses [febrile controls (FCs)] to allow prompt treatment.Methods: Significant independent predictors were identified by applying multivariate logistic regression analyses. A new diagnostic model was constructed and compared with that from diagnostic tests created by other scholars.Results: Data from 10,367 patients were collected. Twelve independent predictors were determined: a lower percentage of monocytes (%MON), phosphorus, uric acid (UA), percentage of lymphocyte (%LYM), prealbumin, serum chloride, lactic dehydrogenase (LDH), aspartate aminotransferase: alanine transaminase (AST: ALT) ratio, higher level of globulin, gamma-glutamyl transpeptidase (GGT), platelet count (PLT), and younger age. The AUC, sensitivity, and specificity of the new model for cross-validation of the KD diagnosis was 0.906 ± 0.006, 86.0 ± 0.9%, and 80.5 ± 1.5%, respectively. An equation was presented to assess the risk of KD, which was further validated using KD (n = 5,642) and incomplete KD (n = 809) cohorts.Conclusions: Children with KD could be distinguished effectively from children with other febrile illnesses by documenting the age and measuring the level of %MON, phosphorus, UA, globulin, %LYM, prealbumin, GGT, AST:ALT ratio, serum chloride, LDH, and PLT. This new diagnostic model could be employed for the accurate diagnosis of KD.

The diagnostic role of AIM2 in Kawasaki disease.

Kawasaki disease (KD), a systemic vasculitis in children, may bring serious complications. However, the etiology of KD remains unclear. AIM2, an intracellular receptor, plays a vital role during the infection caused by a variety of pathogens. However, its role in KD remains unclear. The principal aim of the present research is to concentrate on the relation between AIM2 and KD. We detected the levels of AIM2, IL-18 and IL-1β in all subjects by ELISA. The conventional inflammatory indices were detected in all subjects, such as WBC, HB, CRP and so on. The serum concentrations of AIM2, IL-18 and IL-1β were notably upregulated in the KD group compared to the febrile group and healthy group, respectively. And the three indicators in the KD patients were greatly reduced after interpreted with IVIG. Furthermore, the expressions of IL-18 and IL-1β were positively correlated with AIM2. Meanwhile, the cutoff value of serum AIM2 level for the diagnosis of KD was 541.90ng/L with the specificity of 60% and sensitivity of 92.5%, compared to the febrile controls. And the area under curve (AUC) of AIM2 was 0.771. And no difference was observed in patients with CALs when compared with patients without CALs. The serum AIM2, IL-18 and IL-1β might play a critical role during the progress of KD. AIM2 can be considered as a candidate indicator for Kawasaki disease diagnosis.

The evaluation of vitamin K status in children with febrile seizure.

BackgroundFebrile seizure is the most common neurological disorder in childhood. The exact pathophysiology of febrile seizures is unknown. Recent studies showed the role of vitamin K in nonhematological and inflammatory disorders. This study aimed to investigate the serum vitamin K levels in children with febrile seizures.AimsTo evaluate vitamin K levels in children with febrile seizures.Study DesignProspective case-control study.MethodsThis multicenter study examined representative populations in 8 different cities in Turkey between April 1, 2018 and April 1, 2019. Blood samples were taken from all children at presentation. Vitamin K1, vitamin K2, tumor necrosis factor-alpha, interleukin 1 beta, and interleukin 6 levels were determined by enzyme-linked immunosorbent assay.ResultsA total of 155 children were included in the study—84 children with febrile seizures and 71 children in febrile control group. Serum vitamin K1 and vitamin K2 levels were also higher in children with febrile seizures than in the controls. The results of statistical analysis showed that vitamin K1 and vitamin K2 levels were correlated with tumor necrosis factor-alpha, interleukin 1 beta, and interleukin 6 levels. The median vitamin K1 and vitamin K2 levels of children experiencing their first febrile seizure were higher than those in children with recurrent febrile seizures. Type of febrile seizure has no effect on serum vitamin K1 and vitamin K2 levels.ConclusionIn children with febrile seizures, vitamin K levels are higher than those in the control group. These new findings may contribute to elucidating the etiopathogenesis of febrile seizures.

Identifying Downregulation of Autophagy Markers in Kawasaki Disease.

Kawasaki disease (KD) is the most common cause of heart disease acquired in childhood. Even if treated with high-dose intravenous immunoglobulin G (IVIG) at the early stage; children are still at risk of developing coronary artery lesions. Accumulating evidence suggests that autophagy is enhanced in various heart diseases. Evaluating the pathogenic role of autophagy in KD and coronary artery lesions (CAL) may aid in identifying a potential therapeutic target for the treatment or prevention of the disease. Blood samples were obtained from 20 children with KD at the onset of disease and 21 days after IVIG therapy. Twenty children with other causes of febrile disease and 20 healthy children were included as controls. Total RNA was extracted from white blood cells; and autophagy-related gene mRNA expression levels were measured using real-time polymerase chain reaction. The patients with KD had downregulated levels of LC3B mRNA (0.50 ± 0.06 vs. 1.67 ± 0.15; p < 0.001), BECN 1 mRNA (0.70 ± 0.08 vs. 1.43 ± 0.23; p < 0.05), and ATG16L1 mRNA (0.28 ± 0.04 vs. 0.96 ± 0.16; p < 0.01) compared to the febrile control group. The values of these parameters all increased significantly 21 days after the IVIG therapy as follows: LC3B mRNA (1.77 ± 0.29 vs. 0.50 ± 0.06; p < 0.001), BECN 1 mRNA (1.67 ± 0.36 vs. 0.70 ± 0.08; p < 0.05), and ATG16L1 mRNA (2.96 ± 0.43 vs. 0.28 ± 0.04; p < 0.001), while the level of ATG16L1 mRNA persists low in KD patients with CAL. Our results showed the autophagy-related genes expressions in KD and their change after IVIG administration. This suggests that autophagy may have a protective effect on KD.

The Risk Prediction of Coronary Artery Lesions through the Novel Hematological Z-Values in 4 Chronological Age Subgroups of Kawasaki Disease.

Background and Objectives: Most cases of Kawasaki disease (KD) occur between the ages of 6 months and 5 years. Differences in immunological reaction and CAL (coronary artery lesion) by the age subgroups classified according to the prevalence of KD and those particularly in the earlier life of KD should be investigated. Materials and Methods: The laboratory data of 223 infantile and 681 non-infantile KD cases from 2003 to 2018 at Korea University Hospital were retrospectively analyzed. Patients with KD were divided into infants and non-infants and further subdivided into four subgroups by age. The age-adjusted Z-values were compared among the subgroups. Febrile controls were identified as patients with fever for >5 days and who showed some of the KD symptoms. Results: IVIG (intravenous immunoglobulin) resistance at the age of 6 months or less was significantly lower than that at the ages of 7–12 months and 13–60 months (respectively, p < 0.05). The significant risk factors for CAL in total KD patients were age, incomplete KD, post-IVIG fever, IVIG resistance, convalescent Z-eosinophil, and subacute platelet (p < 0.05). The significant risk factors for CAL at the age of 6 months or less were IVIG resistance, acute Z-neutrophil, subacute Z-neutrophil, subacute NLR (neutrophil to lymphocyte ratio), and subacute platelet (respectively, p < 0.05). Conclusion: Younger age and incomplete presentation in KD can be independent risk factors for CAL. The immune reactions of KD at a younger age are more tolerated compared with those at older ages during the acute phase. The immune response at the age of 6 months or less showed immune tolerance in terms of incomplete presentation and IVIG responsiveness. The risk factors such as IVIG resistance, subacute platelet, subacute NLR, and acute or subacute Z-neutrophil at the age of 6 months or less can be very useful parameters to predict CAL in young, incomplete KD.

Lassa Fever Induced Hearing Loss: The Neglected Disability of Hemorrhagic Fever

ObjectiveLassa fever (LF) a hemorrhagic fever endemic to Western has an incidence of approximately 500,000 cases per year. Here, we evaluate hearing loss and other sequelae following LF. MethodsThis case-control study enrolled laboratory confirmed LF survivors, non-LF Febrile controls and Matched Community controls with no history of LF or recent hospitalization for a febrile illness.Study participants completed a symptom questionnaire. Pure-tone audiometry was completed by a subset of participants. ResultsOne hundred forty-seven subjects were enrolled aged from 3-66 years (mean = 23.3). LF survivors were significantly more likely to report balance difficulties (55% vs 20%, p < 0.001), hair loss (32% vs 7%, p < 0.001), difficulty speaking (19% vs 1%, p < 0.001), social isolation (50% vs 0%, p < 0.001), and hearing loss (17% vs 1%, p = 0.002) in comparison to Matched-Community Controls. Similar trends were noted in comparison to Febrile Controls, although these findings were non-significant. Fifty subjects completed audiometry. Audiometry found that LF survivors had significantly more bilateral hearing loss in comparison to Matched-Community Controls (30% vs 4%, p = 0.029). ConclusionThis study characterizes the sequelae of LF and highlights the need for increased access to hearing care in West Africa.

Biomarkers for the Discrimination of Acute Kawasaki Disease From Infections in Childhood.

Background: Kawasaki disease (KD) is a vasculitis of early childhood mimicking several infectious diseases. Differentiation between KD and infectious diseases is essential as KD's most important complication—the development of coronary artery aneurysms (CAA)—can be largely avoided by timely treatment with intravenous immunoglobulins (IVIG). Currently, KD diagnosis is only based on clinical criteria. The aim of this study was to evaluate whether routine C-reactive protein (CRP) and additional inflammatory parameters myeloid-related protein 8/14 (MRP8/14 or S100A8/9) and human neutrophil-derived elastase (HNE) could distinguish KD from infectious diseases.Methods and Results: The cross-sectional study included KD patients and children with proven infections as well as febrile controls. Patients were recruited between July 2006 and December 2018 in Europe and USA. MRP8/14, CRP, and HNE were assessed for their discriminatory ability by multiple logistic regression analysis with backward selection and receiver operator characteristic (ROC) curves. In the discovery cohort, the combination of MRP8/14+CRP discriminated KD patients (n = 48) from patients with infection (n = 105), with area under the ROC curve (AUC) of 0.88. The HNE values did not improve discrimination. The first validation cohort confirmed the predictive value of MRP8/14+CRP to discriminate acute KD patients (n = 26) from those with infections (n = 150), with an AUC of 0.78. The second validation cohort of acute KD patients (n = 25) and febrile controls (n = 50) showed an AUC of 0.72, which improved to 0.84 when HNE was included.Conclusion: When used in combination, the plasma markers MRP8/14, CRP, and HNE may assist in the discrimination of KD from both proven and suspected infection.

The Platelet microRNA Profile of Kawasaki Disease: Identification of Novel Diagnostic Biomarkers.

Challenging diagnosis and unknown etiology of Kawasaki disease (KD) increase the coronary artery lesions incidence. microRNAs (miRNAs) are the most promising biomarkers because of their stability in peripheral blood and noninvasive measurement procedure, whose potential utility have been proved in cancers. To explore the utility of differentially expressed (DE) miRNAs as early diagnostic markers, 44 patients (25 incomplete KD and 19 complete KD) and 31 febrile controls were recruited for small RNA sequencing. From all the 1922 expressed miRNA, 210 DE miRNAs were found between KD and febrile control groups. Though platelet miRNA profiles of complete KD incomplete KD were much similar through cluster analysis, the DE miRNAs were not identical. Eight DE miRNAs were validated by real-time quantitative PCR (qRT-PCR) in complete or incomplete KD groups using a normalizer, miR-126-3p, which was identified by geNorm and NormFinder tools. The expression level of miRNAs continuous changed over time was observed and the function analysis showed the potential role of miRNAs as therapeutic biomarkers. Additionally, the prediction model for KD showed a sensitivity of 78.8% and a specificity of 71.4%, respectively. This study used small RNA sequencing to identify miRNA biomarkers KD diagnosis based on a large sample size. Our findings shine a light on the understanding of molecular pathogenesis of KD and may improve the accuracy of KD diagnosis and prognosis in clinical.

Circulating microRNAs differentiate Kawasaki Disease from infectious febrile illnesses in childhood

BackgroundKawasaki Disease (KD) is an acute vasculitis of unknown etiology in children that can lead to coronary artery lesions (CAL) in 25% of untreated patients. There is currently no diagnostic test for KD, and the clinical presentation is often difficult to differentiate from other febrile childhood illnesses. Circulating microRNAs (miRNAs) are small noncoding RNA molecules that control gene expression by inducing transcript degradation or by blocking translation. We hypothesize that the expression of circulating miRNAs will differentiate KD from non-KD febrile illnesses in children. MethodsCirculating miRNA profiles from 84 KD patients and 29 non-KD febrile controls (7 viral and 22 bacterial infections) were evaluated. 3 ul of serum from each subject was submitted to 3 freeze/heat cycles to ensure miRNA release from microvesicles or interaction with serum proteins. miRNAs were reverse transcribed using a pool of primers specific for each miRNA. Real-time PCR reactions were performed in a 384 well plate containing sequence-specific primers and TaqMan probes in the ABI7900. ‘. ResultsKD patients (3.6 ± 2.2 yrs., 58% male) were found to have a unique circulating miRNA profile, including upregulation of miRNA-210-3p, −184, and -19a-3p (p < .0001), compared to non-KD febrile controls (8.5 ± 6.1 yrs., 72% male). ConclusionsCirculating miRNAs can differentiate KD from infectious febrile childhood diseases, supporting their potential as a diagnostic biomarker for KD.

Reduction in total leukocytes in malaria patients compared to febrile controls: A systematic review and meta-analysis.

BackgroundLeukocyte alterations are a common hematological alteration among malaria patients.ObjectivesThis systematic review and meta-analysis aimed to provide data and evidence comparing alterations in total leukocyte counts in malaria patients compared to febrile/healthy subjects at baseline before treatment. A systematic review was conducted by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for reporting systematic reviews and meta-analyses.Data sourcesWeb of Science (ISI), Scopus, and Medline.Study eligibility criteria, participants, and interventionsAll published articles reporting a total leukocyte count of patients infected with malaria, non-malaria (febrile or healthy group) at baseline before treatment before August 27, 2019, were retrieved, and data were extracted by two main reviewers independently.Study appraisal and synthesis methodsWe used a forest plot, heterogeneity test (Cochran’s Q), and the degree of heterogeneity (I2) to test whether the included studies were heterogeneous. The quality of the included studies was determined by a quality assessment guide based on the quality assessment tool developed by the Newcastle-Ottawa Scale (NOS). Cochran’s Q (Chi-square) and Moran's I2 were used to evaluate heterogeneity. Meta-regression using STATA software was conducted to find the source of heterogeneity. A funnel plot with Egger’s test was used to examine the significance of publication bias among the included studies. The mean differences were estimated using a random-effects model.ResultsOut of the 2,261 articles screened, 29 articles were included in this systematic review and meta-analysis. The heterogeneity test indicated that there was heterogeneity among the included studies with no publication bias. The meta-analysis demonstrated that the total leukocyte count was significantly lower in patients with malaria (n = 4,619) than in those without malaria (n = 10,056) (Z = 4.0, P-value < 0.00001, mean difference = -1.38, 95% CI = -2.06-(-0.71)). Leukocyte differential alterations, low lymphocyte counts (P-value <0.0001, mean difference = -1.03, 95% CI = -1.53-(-0.53)) and a high NL ratio were found in the malaria group (n = 1,579) compared to the non-malaria group (n = 4,991) (P-value <0.0001, mean difference = 0.6, 95% CI = 0.32–0.88). The subgroup analysis indicated that there was a significantly lower total leukocyte count in the malaria group (n = 3,545) than in the febrile group (n = 8,947) (Z = 1.33, P-value < 0.0001, mean difference = -1.76, 95% CI = -2.56-(-0.96)), but no significant difference was found between the malaria group (n = 1,232) and the healthy group (n = 1,679) (P-value > 0.05).LimitationsAs the specific diagnoses in the febrile groups were not reported in the included studies so that the results of the present study need to be carefully interpreted.Conclusions and implications of key findingsThis systematic review demonstrated that the total leukocyte count was affected by malarial infection at baseline despite the heterogeneity of the included studies. Future work must aim to understand the treatment-related total leukocyte reduction during follow-up or post-treatment outcomes in malaria-endemic settings.

High-Throughput Screening of Kawasaki Disease Sera for Antiviral Antibodies.

Clinical features of Kawasaki disease (KD) display overlap with common pediatric viral illnesses, leading some to hypothesize that a viral infection is the inciting event for KD. To investigate viral infection history in KD patients, we performed comprehensive serological profiling using a high-throughput phage immunoprecipitation sequencing assay covering the complete reference protein sequences of known viruses with human tropism. KD and matched febrile control sera did not demonstrate differences in antiviral antibody profiles. We conclude that in the acute and subacute phases of disease, KD patients do not exhibit serologic evidence of exposure to known viruses that differs from controls.