Monitoring of adenoviremia in pediatric patients undergoing hematopoietic stem cell transplantation: Is it alone sufficient to predict adenoviral disease?

BACKGROUND: We aimed to evaluate our pediatric HSCT recipients routinely monitored for adenoviremia and to determine the adequacy of this monitoring in predicting adenoviral disease (AD). METHODS: A retrospective cohort of patients who underwent allogeneic HSCT between January 2021 and August 2022, and routinely monitored for adenoviremia by real-time PCR was included in our survey. Demographic and clinical data of the patients were recorded. Incidence rates, risk factors, and mortality rates related to adenoviremia, and AD were analyzed. RESULTS: Among 104 HSCTs performed in 94 patients adenovirus (AdV) was revealed in 27 (26%) episodes and adenoviremia in 18 (17.3%) HSCT episodes. AD without adenoviremia developed in nine episodes (8.6%). Disseminated disease was significantly more frequently detected in episodes with adenoviremia (p = .008). GVHD was independent risk factor for AdV detection (OR: 8.6, 95% CI: 2.03-33.7, p = .001). Viremia developed within a shorter time interval after HSCT in isolated episodes of adenoviremia compared to those with concomitant AD (p = .006). Initial and peak viral loads were significantly higher in adenoviremia with AD (p < .001). Mortality was higher in the AdV-detected episodes (p < .001) than in the AdV-undetected episodes. AdV-related mortality was found to be 22.2%. Adenoviremia increased the risk of mortality (OR: 1.2, 95% CI: 0.22-1.33, p = .01). CONCLUSIONS: Adenoviremia monitoring is an important process in the detection of AD. Since some patients may develop AD without accompanying by adenoviremia, monitoring for AdV in blood samples should be supported with other monitoring methods in order to evaluate the probable involvement of different organs or systems.

Antifungal Therapy in Pediatric Acute Lymphoblastic Leukemia: A Single-center Experience.

INTRODUCTION: Invasive fungal infections (IFIs) are significant causes of morbidity and mortality in leukemia patients. This study investigated antifungal treatment and prophylaxis features according to leukemia risk groups and treatment phases in pediatric acute lymphoblastic leukemia (ALL) patients who received Berlin-Frankfurt-Munster-based protocols. MATERIALS AND METHODS: We retrospectively examined ALL patients' data between the ages of 1 and 18 and treated them with Berlin-Frankfurt-Munster-ALL protocols between June 2013 and December 2016. RESULTS: A total of 446 febrile neutropenic attacks in 85 children were evaluated. Seventy-two patients received antifungals in 151 infection attacks, while 13 patients did not receive any antifungal treatment during chemotherapy. Empirical, preemptive, or proven treatments were given to 74.8%, 21.2%, and 4% of patients, respectively. The frequency of antifungal therapy increased linearly and significantly from the standard-risk group to the intermediate-risk (IR) group, high-risk (HR) group, and relapsed group. IR patients needed more antifungal therapy while receiving induction, whereas HR patients needed more throughout the induction and HR consolidation blocks than other phases. During induction, IR patients received antifungal therapy similar to HR patients' treatment in the induction and HR consolidation blocks. CONCLUSIONS: Antifungal therapy requirements increased as the severity and intensity of chemotherapy increased for all leukemia risk groups. The requirement of antifungal therapy for IR patients receiving induction was similar to that of HR patients; further studies are needed to evaluate the potential advantages of using primary antifungal prophylaxis in IR patients.

Intestinal microbiota composition of children with infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and multisystem inflammatory syndrome (MIS-C).

Microbiota composition may play a role in the development, prognosis, or post-infection of COVID-19. There are studies evaluating the microbiota composition at the time of diagnosis and during the course of COVID-19, especially in adults, while studies in children are limited and no study available in children with multisystem inflammatory syndrome in children (MIS-C). This study was planned to compare intestinal microbiota composition in children diagnosed with MIS-C and acute COVID-19 infection with healthy children. In this prospective multicenter study, 25 children diagnosed with MIS-C, 20 with COVID-19 infection, and 19 healthy children were included. Intestinal microbiota composition was evaluated by 16 s rRNA gene sequencing. We observed changes of diversity, richness, and composition of intestinal microbiota in MIS-C cases compared to COVID-19 cases and in the healthy controls. The Shannon index was higher in the MIS-C group than the healthy controls (p < 0.01). At phylum level, in the MIS-C group, a significantly higher relative abundance of Bacteroidetes and lower abundance of Firmicutes was found compared to the control group. Intestinal microbiota composition changed in MIS-C cases compared to COVID-19 and healthy controls, and Faecalibacterium prausnitzii decreased; Bacteroides uniformis, Bacteroides plebeius, Clostridium ramosum, Eubacterium dolichum, Eggerthella lenta, Bacillus thermoamylovorans, Prevotella tannerae, and Bacteroides coprophilus were dominant in children with MIS-C. At species level, we observed decreased Faecalibacterium prausnitzii, and increased Eubacterium dolichum, Eggerthella lenta, and Bacillus thermoamylovorans in children with MIS-C and increased Bifidobacterium adolescentis and Dorea formicigenerasus in the COVID-19 group. Our study is the first to evaluate the microbiota composition in MIS-C cases. There is a substantial change in the composition of the gut microbiota: (1) reduction of F. prausnitzii in children with MIS-C and COVID-19; (2) an increase of Eggerthella lenta which is related with autoimmunity; and (3) the predominance of E. dolichum is associated with metabolic dysfunctions and obesity in children with MIS-C. CONCLUSIONS:  Alterations of the intestinal microbiota might be part of pathogenesis of predisposing factor for MIS-C. It would be beneficial to conduct more extensive studies on the cause-effect relationship of these changes in microbiota composition and their effects on long-term prognosis. WHAT IS KNOWN: • Microbiota composition may play a role in the development, prognosis, or post-infection of COVID-19.  • However, the number of studies on children is limited, and no study on multisystem inflammatory syndrome in children is currently available (MIS-C). WHAT IS NEW: • In individuals with MIS-C, the composition of the gut microbiota changed dramatically. • Decreased Faecalibacterium prausnitzii have been observed, increased Eggerthella lenta, which was previously linked to autoimmunity, and predominance of Eubacterium dolichum which was linked to metabolic dysfunction and obesity.

Potential and promising marker for serious bacterial infections in children: Delta neutrophil index.

AIM: This study aimed to evaluate the usefulness and accuracy of the delta neutrophil index (DNI), an index expressing the number of immature granulocytes as a proportion of the total, as an inflammatory marker in predicting serious bacterial infections (SBIs). METHODS: Paediatric patients admitted to our hospital with fever were divided into four groups: SBI, non-SBI, COVID-19 and control group. White blood cell count, absolute neutrophil count, C-reactive protein and the DNI were recorded, and their accuracy in predicting SBI was evaluated. RESULTS: Mean DNI was 4.96 ± 8.38 in the SBI group (150 patients), 0.67 ± 1.68 in the non-SBI group (397 patients), 0.29 ± 0.99 in the COVID-19 group (112 patients) and 0.14 ± 0.21 in the control group (102 patients). The DNI was significantly higher in the SBI group compared with the non-SBI (P < 0.001); the non-SBI group also had higher levels than the COVID-19 group (P = 0.005). One percent increase in the DNI increased the SBI rate 1.36 times (odds ratio 1.36 (95% confidence interval 1.23-1.49), P < 0.001). Based on the determined cut-off value (>2.5%), the DNI (odds ratio 6.27 (95% confidence interval 3.85-10.21), P < 0.001) significantly predicted SBIs with 90.4% specificity and 47.7% sensitivity. CONCLUSIONS: SBIs in childrenare associated with an increase in DNI levels. Compared to other biomarkers, the DNI had higher specificity in predicting SBIs. The DNI may also be usefulin differentiating bacterial and non-bacterial infections in individualclinical syndromes. Currently, there is no evidence that serum DNI aids indifferentiating COVID-19 and upper respiratory tract infection.

Do parents vaccinated against COVID-19 protect their children from hospitalization due to COVID-19?

OBJECTIVE: This study aimed to determine whether parental vaccination against coronavirus disease 2019 (COVID-19) prevents hospitalization of COVID-19-infected children. METHODS: This study was based on data obtained from the records of pediatric patients that were followed up for virologically proven COVID-19 infection between August and October 2021, during which time the delta variant was dominant in Turkey and the children were isolating at home. RESULTS: There were 151 patients in the inpatient group and 218 in the outpatient group; the mean age was 172.5 and 145.5 months in the groups, respectively. The rates of obesity (22.5% and 6.4%, respectively, p < 0.001) and neurological-neurodevelopmental disorders (8.6% and 1.4%, respectively, p < 0.001) were significantly higher in the inpatient group than in the outpatient group. Of the outpatients' parents, 67.4% (n = 147) were fully vaccinated vs. 38.4% (n = 58) in the inpatient group. In all, 39.7% (n = 60) of the inpatients' parents were unvaccinated vs. 18.3% (n = 40) in the outpatient group. There was a significant correlation between the vaccination status and the patient groups (p < 0.001); it was determined that the COVID-19 infection would be mild in children if both parents were fully vaccinated. When both parents were fully vaccinated against COVID-19, the hospitalization rate decreased and the outpatient follow-up rate increased. CONCLUSION: Having both parents fully vaccinated against COVID-19 can indirectly protect their subsequently infected children from hospitalization and the long-term effects of infection. Nonetheless, more comprehensive research on delta and non-delta variants is needed.

Evaluation of the Clinical and Laboratory Findings of Asthmatic Children with SARS-CoV-2 Infection.

INTRODUCTION: There are a limited number of studies about the clinical findings of coronavirus infection in pediatric patients with asthma. We aimed to evaluate the clinical and laboratory characteristics of pediatric patients with asthma and healthy children without chronic disease who infected with SARS-CoV-2. METHODS: This is a retrospective, case-control study comparing the asthma diagnosed and healthy children who were diagnosed as COVID-19 in our hospital between March 11 and November 10, 2020. RESULTS: During the study period, 6,205 children were diagnosed with CO-VID-19 in our hospital. Only 54 (0.87%) patients had a diagnosis of asthma. The mean of the age was 10.5 years and 53.7% (n:29) of the patients with asthma were male. Cough, shortness of breath, emesis, and diarrhea were found to be significantly higher in asthma group than in the control group (respectively p = 0.002, 0.000, 0.002, 0.019, 0.015). Patients who were given SABA was significantly higher in asthma diagnosed patients (p = 0.000). Hospitalization was significantly higher in asthma group (p = 0.025), and the duration of hospitalization was significantly higher in control group (p = 0.034). There was no significant difference between the 2 groups in terms of requiring oxygen treatment and in laboratory findings between groups. CONCLUSION: This study revealed that pediatric patients diagnosed with asthma were in a mild clinic. According to these findings, asthma may not affect the course of the COVID-19 in children.

Severe Coronavirus Disease Pneumonia in Pediatric Patients in a Referral Hospital.

OBJECTIVE: We aimed to evaluate the characteristics and outcomes of critically ill children managed in an intensive care unit because of coronavirus disease (COVID-19) pneumonia with respiratory support requirements. METHODS: We performed a single-center retrospective observational study in a pediatric intensive care unit (PICU) with 32 beds in Ankara City Hospital, Ankara, Turkey, from 13 March 2020 to 31 December 2020. Patients who needed positive-pressure ventilation (PPV) therapy for COVID-19 pneumonia were included in the study. Demographic, clinical and laboratory data were extracted from the patients' electronic medical records. As outcomes, the hospitalization rate of all pediatric patients diagnosed as having with COVID-19 by Polymerase Chain Reaction(PCR), PICU admission rate for COVID-19 pneumonia among all hospitalized patients, PPV support rate, intensive care hospitalization duration (days), total hospitalization duration (days), survival rate and tracheotomy requirement were evaluated. RESULTS: During the study period, 7033 children tested positive for COVID-19 in PCR tests. Of these patients, 1219 were hospitalized for COVID-19. Seventeen patients needed PPV support because of COVID-19 pneumonia. High proportion (65%) of patients admitted to the PICU had comorbid diseases. Noninvasive ventilation was applied in 15 patients (88%). The hospitalization rate among the children with COVID-19 was 17%, of whom 1.6% were admitted to the PICU. Mortality rates were 0.056% of all the cases and 0.32% of the hospitalized patients in our hospital. CONCLUSION: The presence of a comorbid disease could be a sign of severe disease in children with higher lethality. Very few children required PPV support because of severe COVID-19 pneumonia.

Coronavirus disease (COVID-19) spread from Wuhan, China, and caused an outbreak that threatened human health globally. Reports worldwide have shown that the outbreak mainly affected the adult population. Data about severe COVID-19 pneumonia in children are limited. Treatment interventions for the adult population have been adapted for children. Our article was aimed at building an opinion about this patient group. We found that severe COVID-19 pneumonia occurred in only a small population. Cardiac and neurological comorbidities are associated with higher mortality rates. Only a few patients with COVID-19 required mechanical ventilation support.

Case Report of Severe COVID-19 Pneumonia in a Term Newborn.

Coronavirus disease (COVID-19) has been shown to affect all age groups. The data in the literature usually admit a milder form of disease in infants and newborns than adults. COVID-19 is rarely seen in newborns and an urgent diagnosis should be made in any suspicious situation. A 6-day-old female newborn was admitted to our hospital with fever and dyspnea without cough. A rapid reverse-transcription polymerase chain reaction COVID-19 showed a positive result. Chest computed tomography revealed bilateral and widespread pulmonary involvement. After support therapy, the newborn was successfully discharged. We should carefully consider the new type of coronavirus as an agent for pneumonia in newborns with fever and dyspnea together with non-symptomatic family history. Our case was one of the interesting reported cases of severe pneumonia presenting in the perinatal period.

A purely quantitative form of partial recessive IFN-γR2 deficiency caused by mutations of the initiation or second codon.

Mendelian susceptibility to mycobacterial disease (MSMD) is characterized by clinical disease caused by weakly virulent mycobacteria, such as environmental mycobacteria and Bacillus Calmette-Guérin vaccines, in otherwise healthy individuals. All known genetic etiologies disrupt interferon (IFN)-γ immunity. Germline bi-allelic mutations of IFNGR2 can underlie partial or complete forms of IFN-γ receptor 2 (IFN-γR2) deficiency. Patients with partial IFN-γR2 deficiency express a dysfunctional molecule on the cell surface. We studied three patients with MSMD from two unrelated kindreds from Turkey (P1, P2) and India (P3), by whole-exome sequencing. P1 and P2 are homozygous for a mutation of the initiation codon(c.1A>G) of IFNGR2, whereas P3 is homozygous for a mutation of the second codon (c.4delC). Overexpressed mutant alleles produce small amounts of full-length IFN-γR2 resulting in an impaired, but not abolished, response to IFN-γ. Moreover, SV40-fibroblasts of P1 and P2 responded weakly to IFN-γ, and Epstein Barr virus-transformed B cells had a barely detectable response to IFN-γ. Studies in patients' primary T cells and monocyte-derived macrophages yielded similar results. The residual expression of IFN-γR2 protein of normal molecular weight and function is due to the initiation of translation between the second and ninth non-AUG codons. We thus describe mutations of the first and second codons of IFNGR2, which define a new form of partial recessive IFN-γR2 deficiency. Residual levels of IFN-γ signaling were very low, accounting for the more severe clinical phenotype of these patients with residual expression levels of normally functional surface receptors than of patients with partial recessive IFN-γR2 deficiency due to surface-expressed dysfunctional receptors, whose residual levels of IFN-γ signaling were higher.

Risk factors for bacteremia in children with febrile neutropenia

Background/aim: Bacteremia remains an important cause of morbidity and mortality during febrile neutropenia (FN) episodes. We aimed to define the risk factors for bacteremia in febrile neutropenic children with hemato-oncological malignancies. Materials and methods: The records of 150 patients aged ≤18 years who developed FN in hematology and oncology clinics were retrospectively evaluated. Patients with bacteremia were compared to patients with negative blood cultures. Results: The mean age of the patients was 7.5 ± 4.8 years. Leukemia was more prevalent than solid tumors (61.3% vs. 38.7%). Bacteremia was present in 23.3% of the patients. Coagulase-negative staphylococci were the most frequently isolated microorganism. Leukopenia, severe neutropenia, positive peripheral blood and central line cultures during the previous 3 months, presence of a central line, previous FN episode(s), hypotension, tachycardia, and tachypnea were found to be risk factors for bacteremia. Positive central line cultures during the previous 3 months and presence of previous FN episode(s) were shown to increase bacteremia risk by 2.4-fold and 2.5-fold, respectively. Conclusion: Presence of a bacterial growth in central line cultures during the previous 3 months and presence of any previous FN episode(s) were shown to increase bacteremia risk by 2.4-fold and 2.5-fold, respectively. These factors can predict bacteremia in children with FN.

[Multicenter investigation of bufavirus in the etiology of viral central nervous system infections of adults and children]. / Bufavirusun çocuklar ve eriskinlerdeki viral santral sinir sistemi enfeksiyonlarinin etiyolojisi açisindan çok Mmerkezli olarak arastirilmasi.

Bufavirus (BuV) is a newly-identified parvovirus in the family of Parvoviridae. Metagenomic analysis of fecal samples from children in Burkina Faso with acute diarrhea showed a highly divergent parvovirus, which was named bufavirus (BuV). The global distribution, epidemiology and genetic characteristics of BuVs infections are obscure. It was first discovered as an agent causing gastroenteritis but the association of BuV infections with various clinical presentations mostly remain to be explored. The aims of this study were to investigate probable impact of BuV in central nervous system infections in a region where it was previously reported to cause human infections and to detect enteroviruses (EV) which are reported as a cause of central nervous system infections in our country. The study was undertaken in three institutions in Ankara province, Central Anatolia, Turkey. Patients, clinically diagnosed with febrile disease and/or central nervous system infections of presumed viral etiology, were enrolled in the study with informed consent. Cerebrospinal fluid specimens were collected from 93 children attended to Gazi University Hospital and Diskapi Yildirim Beyazit Hospital from October 2011-April 2015 and 33 adult patients, attended to Hacettepe University Hospital from June 2012 to March 2013. Clinical history and follow-up, physical examination and standard laboratory findings of the patients were recorded. Nucleic acid extraction was performed via commercially available spin-column assays and complementery DNA (cDNA) synthesis was performed by using commercially available cDNA synthesis kit with randomised hexamer primers. BuV detection was carried out by in house nested-polymerase chain reaction (PCR) utilized with previously-described primers. EV detection was carried out by in house PCR with pan-enterovirus primers. Seventy-four percent (93/126) and 26% (33/126) of the patients were children (0-18) and adults (19-86), respectively. In all patients, bacterial, mycobacterial and fungal cultures were negative, as well as PCR for herpes simplex virus (HSV) types 1 and 2. PCR results of all samples were negative for BuV and EV. This is the first study that evaluates a probable association of BuV and central nervous system infections. Although Parvovirus B19, a well-characterized human pathogen can rarely cause encephalitis, our findings did not confirm such an association for BuV in this preliminary investigation. However, long-term evaluation of individual cases with unknown etiology is required to reveal the relationship of the virus with specific environments.

Tularemia in children, Turkey, September 2009-November 2012.

Tularemia, a zoonotic disease caused by Francisella tularensis, is found throughout most of the Northern Hemisphere. It is not well known and is often misdiagnosed in children. Our aim with this study was to evaluate the diagnosis, treatment, and prognosis for 100 children with tularemia in Turkey. The mean patient age was 10.1 ± 3.5 years (range 3-18 years), and most (63%) patients were male. The most common physical signs and laboratory findings were cervical lymphadenopathy (92%) and elevated erythrocyte sedimentation rate (89%). Treatment response was higher and rate of relapse lower for children 5-10 years of age than for those in other age groups. Associated with treatment failure were female sex, treatment delay of ≥16 days, and use of doxycycline. Tularemia is endemic to Turkey, and the number of cases has been increasing among children as well as adults.

Evaluation of 98 immunocompetent children with cytomegalovirus infection: importance of neurodevelopmental follow-up.

UNLABELLED: This study aims to analyze and evaluate the clinic and demographic features of immunocompetent children that have been diagnosed with cytomegalovirus (CMV) infection. The data of children diagnosed with CMV infection between January 2005 and December 2010 and their follow-ups for 2 years were retrospectively evaluated. Ninety-eight patients were included, and the median age at admission was 5.6 months (5 days-36 months). 54.1% was male. The diagnosis of CMV infection was performed by measurement of serum anti-CMV specific Ig M and IgG titers and PCR method in blood and/or urine. In 3.06% of the patients, congenital infection was detected, whereas possible congenital infection was observed in 36.7% of the patients. Furthermore, 44 patients (44.8%) were detected to have perinatal infection while postnatal infection was spotted in 15.3% of the patients. The common presenting manifestations were prolonged jaundice, diarrhea, vomiting, abdominal distension, skin eruption, and seizure. And the most common physical examination findings were hepatosplenomegaly, microcephaly, jaundice, and petechia. The mainstream laboratory results were elevated transaminases (50%), anemia (30.6%), leukocytosis (27.5%), and thrombocytopenia (18.3%). There were intracranial calcification in 5.1% and eye findings in 5.1%. On follow-up of patients, complete improvement (59.1%), neuromotor developmental delay (11.2%), epilepsy (10.2%), hearing loss (3.06 %), hemolytic anemia (2.04%), and growth retardation (1.02%) were detected. CONCLUSION: CMV infection is a significant disease both in congenital and perinatal period. It must be considered that diagnosed patients need to be monitored for a long time with special attention to their neurodevelopmental follow-ups.

[Invasive pneumococcal disease in two non-vaccinated pediatric cases: pleural empyema and bacteremia]. / Asisiz iki çocuk olguda invazif pnömokokal hastalik: Plevral ampiyem ve bakteriyemi.

Streptococcus pneumoniae, a gram-positive diplococcus, is the causative agent of invasive pneumococcal diseases (IPDs) characterized by severe infections such as bacteraemia, sepsis and meningitis. S.pneumoniae and IPDs are situated in the focus of the vaccine studies because of being encompassed of a significant burden of disease in the world, severe mortality and morbidities, and location in vaccine-preventable diseases group. Although S.pneumoniae has more than 90 defined serotypes, certain serotypes are often identified as the cause of IPDs. Individuals with comorbid and chronic diseases, primary or secondary immune deficiencies, and <2 years or >65 years of age are at increased risk for IPDs. Currently, a 23-valent polysaccharide vaccine and also 7, 10 and 13 valent pneumococcal conjugated vaccines (PCV) have been produced for pneumococci. Phase studies of protein based vaccines, which will provide protection independent of serotypes, and 15-valent pneumococcal conjugated vaccine are still ongoing. In Turkey, in November 2008 PCV7 and in April 2011 PCV13 have been implemented in the national immunization program. First case of the pneumococcal unvaccinated cases presented in this report was a 6-year-old girl patient with pneumonia and pleural empyema due to S.pneumoniae serotype 1, without any underlying risk factors. The other case is a 52-days-old male patient, who had a history of pneumococcal septicemia in the newborn period and was followed for bacteremia associated S.pneumoniae serotype 12B and diagnosed as complement deficiency on follow-up. S.pneumoniae serotype 1 is within serotypes covered by 10 and 13 valent pneumococcal conjugate vaccines and pneumococcal polysaccharide vaccine that are in use today, and is a highly invasive strain often isolated in pneumococcal lobar pneumonia and empyema. S.pneumoniae serotype 12B is a non-vaccine serotype not included in any of conjugate and polysaccharide vaccines, and usually obtained in respiratory infections and nasopharyngeal carriage studies. The first case of this report was presented because of an IPD with a serotype included in PCV13 implemented in the routine childhood vaccination schedule and to give an idea about pneumococcal strains circulating in the community. The second case was discussed to draw attention for the evaluation of immune deficiencies and other risk factors in recurrent infections with encapsulated bacteria such as pneumococci. Pneumococcal conjugate vaccines contribute the public immunity with the reduction of vaccine-type pneumococcal nasopharyngeal carriage, IPD incidence, and IPD associated morbidity and mortality especially in young children, at the same time cause a decrease in the prevalence of antibiotic-resistant infections. Application of the pneumococcal conjugate vaccines covering the whole society is important, according to all these important results.

A perinatal cytomegalovirus infection in an immunocompetent patient with chorioretinitis.

Cytomegalovirus (CMV) infection is the most common viral infection of newborns in all periods worldwide. Perinatal form of infection is usually less severe than the congenital form because of having a lower rate for serious organ involvement like central nervous system. In this article, we report a 3-month-old immunocompetent patient who was diagnosed as having perinatal CMV infection with a scar of chorioretinitis after presenting with gastroenteritis and hepatitis.