Epidemiological Profile of Acute Viral Encephalitis in a Sample of Egyptian Children

INTRODUCTION: Acute encephalitis syndrome (AES) is a considerable public health problem.AIM: This study was designed to describe the aetiology, demographic features, clinical picture, short-term outcome and risk factors of mortality of children with viral encephalitis in Egyptian children.METHODS: PCR detection of viruses in the CSF of pediatric patients admitted to the pediatric unit or ICU Cairo University Pediatric hospital presenting with encephalitis syndrome.RESULTS: Of the 96 patients included in the study, viral etiological agents were detected in 20 cases (20.8%), while 76 patients (79.2%) had no definite viral aetiology. The most abundant virus detected was Enterovirus (EV) in fourteen (14.5%), two (2.1%) were positive for human herpes simplex virus 6 (HSV-6), one (1.0%), human herpes simplex virus1 (HSV-1), one (1.0%) Epstein Barr virus (EBV), one (1.0%), cytomegalovirus (CMV) and one (1.0%) with varicella-zoster virus (VZV). On the short term outcome, 22 (22.9) patients died, and 74 (77.1%) survived. Severity outcome among survival was vegetative in three cases (4%) severe in 9 (12.16%), moderate in 14 (18.9%), mild in 29 (39.2%) and full recovery in 19 (25.6%). Mortality risk factors for younger age, the presence of apnea, the need for mechanical ventilation and the presence of abnormal CT findings were all significantly associated with fatal outcome (p < 0.05).CONCLUSION: Enterovirus was the most common cause of encephalitis among Egyptian children. Mortality was correlated with younger age and disease severity at admission. Sequelae were high among infected children

Serum Amyloid A Level in Egyptian Children with Familial Mediterranean Fever

Background and Objectives. SAA is an acute-phase reactant detected during an FMF attack or other inflammatory conditions. High SAA levels may increase the risk of amyloidosis. The aim of the study is to measure the serum amyloid A (SAA) level in a group of Egyptian children with familial Mediterranean fever (FMF) and study its various correlates, if any. Methods. The study enrolled seventy-one children with FMF. Results. SAA level was high in 78.9% of the studied patients with a mean of 81.62±31.6 mg/L, and CRP was positive in 31% of patients. There was no significant releation between SAA level and any demographic or clinical manifestation. High SAA was more frequent in V726A allele (16.9%) followed by M694V allele (12.3%). Elevated SAA levels were more frequent in patients on low colchicine doses. Forty-five percent (45%) of patients have low adherence to colchicine therapy. Interpretation and Conclusion. High SAA levels were detected two weeks after last FMF attack in a large percentage of Egyptian FMF children. This indicates that subclinical inflammation continues during attack-free periods, and SAA could be used as a marker of it

Relevance of hypocapnia to febrile seizures in children

Background: Febrile seizure is the most common type of convulsion in children. However, there are scanty data on the mechanism of its development. The aim of this study was to evaluate the venous blood gas status in children with febrile seizures and to determine whether hypocapnia secondary to hyperthermia-induced hyperventilation was associated with febrile seizures in children. Patients and methods: The study enrolled 43 individuals, twenty-two children with febrile seizures, together with 21 controls (children with febrile illness without seizures). Venous blood gases were determined in the febrile seizure group within 1 h and at 24 h after a seizure attack while, venous blood gases were measured once in the control group within 1 h after a febrile period. Results: There were significant differences in mean blood pH and Pco2 between the febrile seizure and control groups (p < 0.001). There was no significant difference in pH values between the children with complex febrile seizure and those with simple febrile seizure. However, children with complex febrile seizure had significantly lower Pco2 within 1 h of seizure attack than those with simple febrile seizure. In addition, there was a significant correlation between duration of the seizure attack and Pco2 value within 1 h of seizure. Conclusion: The results of the present study confirmed the association between febrile seizure and hypocapnia and that supported the role of hypocapnia in the development of febrile seizures

Toll-like receptor-4 gene variations in Egyptian children with familial Mediterranean fever

Abstract Background Familial Mediterranean fever (FMF) is an autosomal recessive disorder affecting people in the region of the Mediterranean Sea. It is usually associated with mutation in Mediterranean fever (MEFV) gene that encodes the pyrin protein, which affects the innate inflammatory response. Toll-like receptors (TLR) are a family of pattern recognition receptors that recognize pathogenic microbes and activate antimicrobial defense mechanisms. Toll-like receptor 4 (TLR-4) is concerned with recognition of gram-negative organisms. There is growing clinical evidence suggesting a role for expression of TLRs in the immune pathogenesis of FMF. Thus, the aim of the current study was to evaluate the presence of TLR-4 (p.Asp299Gly) and TLR-4 (p.Thr399Ile) gene variants in association with Egyptian children having FMF, furthermore, its effect on disease course and severity. Results Seventy Egyptian children diagnosed as having FMF, together with 50 age and gender-matched controls were enrolled in the study. The TLR-4 (p.Asp299Gly) and (Thr399Ile) gene variants were determined by PCR-RFLP analysis for all studied patients and controls. TLR-4 p.Asp299Gly gene variant was detected in 1 (1.4%) of the patients and p.Thr399Ile gene variant was detected in 2 (2%). None of the controls had any of the two tested gene variants. All found variations were heterozygous. We could not find a statistically significant association with disease severity in cases with or without TLR-4 gene variants (P = 0.568). Patients with M694V gene mutation showed a higher disease severity (P = 0.035). Conclusion TLR-4 (p.Asp299Gly) and (p.Thr399Ile) gene variants were not found to have a link with the occurrence, the clinical picture of FMF, its severity, and response to colchicine treatment in Egyptian children. M694V gene mutation seems to be associated with higher disease severity. Further larger studies are needed to verify these results

Relevance of application of the Yamaguchi criteria for patients with suspected juvenile idiopathic arthritis in the absence of arthritis symptoms

Aim of the study: Systemic juvenile idiopathic arthritis (sJIA) is characterized by systemic inflammation beside arthritis. Many children may have delayed onset of arthritis. We aimed in our study to determine whether the Yamaguchi criteria (for adult onset Still’s disease) can be applied in diagnosis of sJIA, especially in absence of arthritis. Material and methods: The cross-sectional study included 30 patients diagnosed with sJIA, those patients diagnosed by the treating paediatrician with ‘definite’ sJIA (fulfilling the International League of Associations for Rheumatology [ILAR] classification criteria) or ‘suspected’ sJIA (not fulfilling the ILAR criteria). The fulfilment of the variables in both the ILAR criteria and the Yamaguchi criteria was recorded for each patient at the time of first presentation. Results: We included 16 boys and 14 girls. Ten patients were diagnosed with suspected sJIA due to the presence of typical systemic features but failed to fulfil the ILAR criteria, especially absence of arthritis in 9 of them. Yamaguchi criteria were fulfilled in a higher number of patients (23/30, 76.7%) as compared to those who fulfilled the ILAR criteria (20/30, 66.7%). All 10 patients with suspected sJIA fulfilled the Yamaguchi criteria, and 11 patients (36.7%) had delayed onset of arthritis. Overall, the 30 patients (100%) in the present study fulfilled either ILAR criteria or Yamaguchi criteria. Conclusions : There is a subgroup of patients with sJIA in whom arthritis is absent or delayed. The use of the Yamaguchi criteria in this subgroup of patients may be useful for early diagnosis and treatment of sJIA. Thus, further studies are needed to integrate supplementary criteria that increase the strength of both the Yamaguchi and the ILAR criteria

Promising roles of erythropoietin and lymphotoxin alpha in critical illness: A pilot study in critically ill children

Background: Several studies proved the anti-inflammatory role of erythropoietin. Little is known about the anti-inflammatory role of lymphotoxin alpha (LT-α). This study was designed to investigate the patterns of erythropoietin (EPO) and LT-α levels in children with acute critical illness. Patients and methods: Thirty-two critically ill children were prospectively subjected to serial estimation of EPO and LT-α levels, during the first 10 days of admission to one of the pediatric intensive care unit of Cairo University. Thirteen healthy children served as control. Results: Serial EPO and LT-α measurements showed significant increases over time early in their critical illness (P < 0.001, respectively). Both cytokines showed significant increases in survivors (P < 0.001, respectively). Kaplan Meier survival analysis revealed a significant increase in mortality with LT-α levels below 108.7 pg/ml, (P < 0.01) on admission. However, EPO did not show any significant difference between survivors and non-survivors. For both LT-α and EPO, levels at day 1 showed a significant decrease in septic patients. EPO levels were significantly elevated on day 1 of admission in non-anemic [mean hemoglobin level (11.8 ± 0.9) g/dL, mean EPO level (110.85 ± 44.5) mIU/ml] compared with anemic patients [mean hemoglobin level (9.3 ± 1.3) g/dL, mean EPO level (69.84 ± 30.763) mIU/ml], 95% CI [13.896–68.112], P < (0.01). Conclusions: Both EPO and LT-α showed significant increment in critically ill children especially in survivors. Our data strongly suggest that, LT-α may have an anti-inflammatory role in children with acute critical illness

Mean Platelet Volume and Splenomegaly as Useful Markers of Subclinical Activity in Egyptian Children with Familial Mediterranean Fever: A Cross-Sectional Study

Objective. To study whether mean platelet volume (MPV) and splenomegaly could be used as subclinical inflammatory markers in children with familial Mediterranean fever (FMF) at the attack-free period. Patients and Methods. The study included ninety-seven children with FMF. MPV was carried out within 4 hours of blood sampling according to standard laboratory practice. Splenomegaly was determined by abdominal ultrasound (USG). Results. High MPV was detected in 84.45% of our studied patients and was significantly higher in FMF patients with splenomegaly than in patients without splenomegaly. There was a statistically significant correlation between MPV and splenic span (P=0.045). Conclusion. Elevated MPV and its significant correlation with splenic span in FMF children during the attack-free periods support the use of MPV and splenomegaly as useful markers of the subclinical inflammation in FMF patients at the attack-free period

Etiologia da hiperglicemia em crianças críticas e o impacto da disfunção de órgãos

RESUMO Objetivo: Verificar a incidência da hiperglicemia de estresse em crianças em condição grave e investigar a etiologia da hiperglicemia com base em um modelo de avaliação da homeostasia. Métodos: Estudo prospectivo de coorte, conduzido em uma unidade de terapia intensiva pediátrica da Cairo University, que incluiu 60 crianças com doença grave e 21 controles saudáveis. Utilizaram-se os níveis séricos de glicose, insulina e peptídeo C, avaliados em até 24 horas após a admissão. O modelo de avaliação da homeostasia foi utilizado para analisar a função das células beta e a sensibilidade à insulina. Resultados: A hiperglicemia foi estimada em 70% dos pacientes. Valores de glicemia ≥ 180mg/dL se associaram com desfechos piores. Os níveis de glicemia se correlacionaram de forma positiva com o Pediatric Risk for Mortality (PRISM III) e o número de órgãos com disfunção (p = 0,019 e p = 0,022, respectivamente), enquanto os níveis de insulina se correlacionaram de forma negativa com o número de órgãos com disfunção (r = -0,33; p = 0,01). O modelo de avaliação da homeostasia revelou que 26 (43,3%) das crianças em condições graves tinham baixa função de células beta e 18 (30%) baixa sensibilidade à insulina. Detectou-se patologia combinada em apenas dois (3,3%) pacientes. Baixa função de células beta se associou de forma significante com a presença de disfunção de múltiplos órgãos, disfunção respiratória, cardiovascular e hematológica, e presença de sepse. Conclusões: A disfunção de células beta pareceu ser prevalente em nossa coorte e se associou com disfunção de múltiplos órgãos

Comparing D-dimer status in children with familial Mediterranean fever during and in between acute attacks

Aim of the work: To compare the D-dimer status in children with familial Mediterranean fever (FMF) during, and in between acute attacks. Patients and methods: The study included 50 children with FMF classified into group I (15 patients during acute attack) and group II (35 patients during attack free period) as well as and 20 matched controls. D-dimer was determined in all study population. Pattern and type of FMF gene mutation were reported from patients’ files. Results: The mean age of the patients was 8.7 ± 2.8 years, disease duration 4.4 ± 2.5 years and they were 28 males:22 females (1.3:1). In group I, the erythrocyte sedimentation rate (48.5 ± 28.6 mm/1st h) and aspartate transaminase (28.5 ± 5 U/L) were significantly increased compared to group II (26.6 ± 14.7 mm/1st h and 25.7 ± 2.7 U/L; p = 0.012 and p = 0.014 respectively). Positive D-dimer was significantly reported in 72% of FMF patients compared with 35% of control (p = 0.006). There was significant difference between frequency of positive D-dimer in group I (86.7%) and group II (65.7%) compared to (35%) in control (p = 0.005 and p = 0.048, respectively), without a significant difference in D-dimer frequency between group I and group II patients (p = 0.18). Fever and abdominal pain were significantly more frequent in patients with positive (100% and 97.2%) compared to negative D-dimer (78.6% and 71.4%) (p = 0.02). No significant association was found between positive D-dimer and specific types of MEFV gene mutation. Conclusion: D-dimer was significantly positive in FMF patients compared to control. These results raise the possibility of thrombosis in FMF patients regardless the presence or absence of acute attack. Keywords: Children, D-dimer, Familial Mediterranean fever, Hypercoagulabilit

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old