Targeted Genotyping of MIS-C Patients Reveals a Potential Alternative Pathway Mediated Complement Dysregulation during COVID-19 Infection.

Complement dysregulation has been documented in adults with COVID-19 and implicated in relevant pediatric inflammatory responses against SARS-CoV-2. We propose that signatures of complement missense coding SNPs associated with dysregulation could also be identified in children with multisystem inflammatory syndrome (MIS-C). We investigated 71 pediatric patients with RT-PCR validated SARS-CoV-2 hospitalized in pediatric COVID-19 care units (November 2020-March 2021) in three major groups. Seven (7) patients suffered from MIS-C (MIS-C group), 32 suffered from COVID-19 and were hospitalized (admitted group), whereas 32 suffered from COVID-19, but were sent home. All patients survived and were genotyped for variations in the C3, C5, CFB, CFD, CFH, CFHR1, CFI, CD46, CD55, MASP1, MASP2, MBL2, COLEC11, FCN1, and FCN3 genes. Upon evaluation of the missense coding SNP distribution patterns along the three study groups, we noticed similarities, but also considerably increased frequencies of the alternative pathway (AP) associated with SNPs rs12614 CFB, rs1061170, and rs1065489 CFH in the MIS-C patients. Our analysis suggests that the corresponding substitutions potentially reduce the C3b-inactivation efficiency and promote slower and weaker AP C3bBb pre-convertase assembly on virions. Under these circumstances, the complement AP opsonization capacity may be impaired, leading to compromised immune clearance and systemic inflammation in the MIS-C syndrome.

De novo HBV Hepatitis in a Child with Liver Transplantation.

Background: Omental torsion (OT) presents as a rare, infrequent pathology with often non-specific symptoms. This condition occurs when the greater omentum is twisted around its axis, producing perfusion defects and vascular impairment of the organ. This case report describes an overweight 26-year-old Caucasian man presenting with acute abdomen in previous appendectomy, whose definitive surgical diagnosis was omental torsion. Omental torsion is a rare pathology regarding the causes of acute abdomen associated with a challenging diagnosis. Case report: We report about a female toddler with liver transplantation due to extrahepatic biliary atresia, who was detected to have positive HBsAg, 27 months after transplantation. Before liver transplantation, routine serologic assessments were negative for HBV infection, the child was vaccinated with three doses of HBV vaccine and developed seroprotective Abs titers. Organ donor was the father, who was negative for HBV infection had negative anti-HBc and had seroprotective titers of anti HBs. A PCR assay in our patient revealed the presence of serum HBV DNA with an increased viral load. The patient started antiviral treatment with Entecavir and had serological response within three months, showing elimination of serum HBV DNA and HBsAg values. Serological investigation of all family members and information from the transplantation unit did not reveal the infection source. Conclusion:de novo Hepatitis B in liver recipients is a rare phenomenon. In donor positive anti-HBc cases, it appears as reactivation of HBV infection. There are very few published cases in which recipients developed de novo HBV hepatitis, despite seronegative HBcAb donors. Caregivers should always be alert for de novo hepatitis B in liver transplanted children as loss of immunity could be an unexpected phenomenon, despite pre-transplant negative serology of the donor and recipient as so as despite seroprotective Abs titers after immunisation of the recipient.

Epstein-Barr Encephalitis in a Child with Congenital Human Immunodeficiency Virus Infection: A Case Report Calling for No Forgetfulness.

BACKGROUND: In resource-rich settings, the rate of mother-to-child transmission of human immunodeficiency virus (HIV) has dramatically decreased by virtue of a combination of preventive strategies during the last two decades. CASE PRESENTATION: We present a case of progressive developmental milestone loss in a toddler with previously unknown congenitally acquired human immunodeficiency virus (HIV) infection, complicated by an Epstein-Barr virus (EBV) coinfection. CONCLUSION: Our report underscores the differential diagnosis between HIV encephalopathy and EBV encephalitis and the vertical transmission of the HIV infection, which constitutes an alarming issue in terms of public health.

Cluster-distinguishing genotypic and phenotypic diversity of carbapenem-resistant Gram-negative bacteria in solid-organ transplantation patients: a comparative study.

Purpose. Solid-organ transplant recipients may display high rates of colonization and/or infection by multidrug-resistant bacteria. We analysed and compared the phenotypic and genotypic diversity of carbapenem-resistant (CR) strains of Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii isolated from patients in the Solid Organ Transplantation department of our hospital.Methodology. Between March 2012 and August 2013, 56 CR strains from various biological fluids underwent antimicrobial susceptibility testing with VITEK 2, molecular analysis by PCR amplification and genotypic analysis with pulsed-field gel electrophoresis (PFGE). They were clustered according to antimicrobial drug susceptibility and genotypic profiles. Diversity analyses were performed by calculating Simpson's diversity index and applying computed rarefaction curves.Results/Key findings. Among K. pneumoniae, KP-producers predominated (57.1 %). VIM and OXA-23 carbapenemases prevailed among P. aeruginosa and A. baumannii (89.4 and 88.9 %, respectively). KPC-producing K. pneumoniae and OXA-23 A. baumannii were assigned in single PFGE pulsotypes. VIM-producing P. aeruginosa generated multiple pulsotypes. CR K. pneumoniae strains displayed phenotypic diversity in tigecycline, colistin (CS), amikacin (AMK), gentamicin (GEN) and co-trimoxazole (SXT) (16 clusters); P. aeruginosa displayed phenotypic diversity in cefepime (FEP), ceftazidime, aztreonam, piperacillin, piperacillin-tazobactam, AMK, GEN and CS (9 clusters); and A. baumannii displayed phenotypic diversity in AMK, GEN, SXT, FEP, tobramycin and rifampicin (8 clusters). The Simpson diversity indices for the interpretative phenotype and PFGE analysis were 0.89 and 0.6, respectively, for K. pneumoniae strains (P<0.001); 0.77 and 0.6 for P. aeruginosa (P=0.22); and 0.86 and 0.19 for A. baumannii (P=0.004).Conclusion. The presence of different antimicrobial susceptibility profiles does not preclude the possibility that two CR K. pneumoniae or A. baumannii isolates are clonally related.

Epidemiological surveillance of multidrug-resistant gram-negative bacteria in a solid organ transplantation department.

BACKGROUND: We assessed the impact of intensified infection control measures (ICM) on colonization and infection caused by carbapenem-resistant (CR) Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii in a solid organ transplantation (SOT) department. METHODS: A quasi-experimental methodology was followed. The study was divided into three periods: pre-intervention, intervention with implementation of an ICM bundle including active surveillance program (ASP) and gradually enhanced measures, and post-ASP without ASP. The bundle included active surveillance cultures, contact precautions, hand hygiene, education of health care workers (HCWs), monitoring of compliance, and environmental cleaning. Incidence of colonization and infection caused by CR gram-negative bacteria was recorded. Molecular analysis of CR bacteria was performed for a certain period. RESULTS: During the intervention, incidence of colonization reduced from 19% to 9% (P<.001). The compliance of HCWs with contact precautions and hand hygiene also improved. Monthly incidence of infections caused by these CR bacteria increased from 2.8 to 6.9/1000 bed-days (P<.001). However, this increase did not have such a strong trend after the intervention. Most K. pneumoniae isolates, the commonest pathogen, carried the blaKPC gene. Colonization and infection rates by CR K. pneumoniae, P. aeruginosa, and A. baumannii were high among SOT recipients. CONCLUSION: In settings where CR gram-negative bacteria are endemic, colonization and infection rates by these bacteria are high among SOT recipients. Implementation of enhanced ICM in all related units of a hospital, although challenging, reduces colonization rates by CR gram-negative bacteria.

Successful management of an outbreak due to carbapenem-resistant Acinetobacter baumannii in a neonatal intensive care unit.

UNLABELLED: The investigation and successful management of a monoclonal Acinetobacter baumannii outbreak in a neonatal intensive care unit are described. Upon the first clustered carbapenem-resistant A. baumannii (CRAB) infections, a bundle of actions were taken, including enhanced infection control, active surveillance (weekly stool samples), case-control study, staff education, daily audits and discontinuation of new admissions. Between September and December 2011, eight neonates developed 10 CRAB infections (five blood, four respiratory and one eye). A total of 216 active surveillance cultures were obtained from 96 neonates (43 % had ≥2 samples). During weeks 12, 16 and 17, active surveillance detected 3, 1 and 2 new CRAB acquisitions, respectively. Prevalence of infections/colonizations decreased, and no event occurred after 20th week. A colonized neonate developed CRAB sepsis and died. All CRAB isolates harboured bla OXA-58 and the intrinsic chromosomal bla OXA-51 carbapenemase genes. CONCLUSION: Active surveillance and enhanced infection control measures effectively contained spread of CRAB clone in the neonatal intensive care unit.

Tuberculous meningitis in Greek children.

BACKGROUND: Tuberculous meningitis (TBM) is the most severe form of Mycobacterium tuberculosis infection. Our aim was to analyze the epidemiology, clinical features, diagnostic approach, and outcome of tuberculous meningitis in childhood. METHODS: During a 25-y period (1984-2008), 43 children, aged 7 months to 13 y, were hospitalized in the Paediatric Department of the referral centre for infectious diseases in Thessaloniki, Greece with the diagnosis of TBM. The patients were classified according to the clinical findings on admission as per the UK Medical Research Council (MRC) staging: stage I, 16/43 (37.2%) children; stage II, 16/43 (37.2%); and stage III 11/43 (25.6%). RESULTS: Twenty-seven of the 43 patients were Greek (63%) and none had been BCG-vaccinated. A family history of tuberculosis was identified in 18 cases (42%). 35 patients (81%) had a positive tuberculin skin test. An extrameningeal site of infection was identified in 14 children (33%); pulmonary tuberculosis in 14/43 patients (5/13 miliary tuberculosis) and spondylitis in 1. All patients were treated with anti-tuberculous drugs and 36 (84%) also received corticosteroids. Complications during hospitalization (coma, seizures, cranial nerve palsy, hydrocephalus) presented in 26 patients (60%). Two patients died (5%) and 6 (14%) had permanent neurological sequelae. CONCLUSION: TBM, although rare, remains a disease with significant morbidity and mortality. Early clinical diagnosis and appropriate treatment initiation are important for the prognosis.