Immunocompromised Children Research Articles

Simultaneous quantitation of favipiravir and its hydroxide metabolite in human plasma and hamster matrices using a UPLC-MS/MS method.

Favipiravir, a broad-spectrum RNA-dependent RNA polymerase inhibitor, is currently being evaluated in preclinical and clinical studies for the treatment of various infectious diseases including COVID-19. We developed an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay for the quantification of favipiravir and its hydroxide metabolite (M1), in human and hamster biological matrices. Analytes were separated on an Acquity UPLC HSS T3 column (2.1 × 100 mm, 1.8μm) after a simple protein precipitation with acetonitrile. The mobile phase consisted of water and methanol, each containing 0.05% formic acid. Experiments were performed using electrospray ionization in the positive and negative ion mode, with protonated molecules used as the precursor ion and a total run time of 6min. The MS/MS response was linear over the concentration ranges from 0.5-100 μg/ml for favipiravir and 0.25-30 μg/ml for M1. Intra- and inter-day accuracy and precision were within the recommended limits of the European Medicines Agency guidelines. No significant matrix effect was observed, and the method was successfully applied to inform favipiravir dose adjustments in six immunocompromised children with severe RNA viral infections. In conclusion, the UPLC-MS/MS assay is suitable for quantification of favipiravir over a wide range of dosing regimens, and can easily be adapted to other matrices and species.

Carbapenem-Resistant Enterobacteriaceae Infection in Immunocompromised Children with CRE Colonization: Incidence and Outcomes in an Antibiotic-Limited Setting

Objective: To determine the incidence of carbapenem-resistant Enterobacteriaceae (CRE) infection in patients with CRE colonization and compare the treatment outcomes between febrile patients with non-septic presentation who received empirical treatment with meropenem and those who did not. Material and Methods: The medical records of febrile patients with CRE colonization aged <15 years who were hospitalized at Songklanagarind Hospital between January 2018 and December 2020 were reviewed. Results: Among the 61 patients with CRE colonization, CRE infection was identified during eight febrile episodes in six patients (9.8%). Hematologic malignancies, solid tumors, and other diseases were diagnosed in 21 (34.4%), 25 (41.0%), and 15 (24.6%) patients, respectively. The median (interquartile range [IQR]) duration from CRE colonization to the first episode of fever was 22 (1.8–60.8) days. Among the 82 febrile episodes without initial sepsis or central nervous system infection, 19 and 63 episodes, respectively, were initially treated with meropenem and non-carbapenems. Treatment outcomes—including the proportion of patients needing step-up antibiotics (21.1% vs. 36.5%), development of sepsis (5.3% vs. 15.9%), and death within 30 days (6.6% vs. 9.8%) - were not significantly different between the two groups.Patients who developed sepsis had significantly higher resistance to empirical antibiotics (75% vs. 26.3%) as well as a significantly higher incidence of severe neutropenia lasting more than one week (85.7% vs. 21.9%) than those without sepsis.Conclusion: Patients with CRE colonization who exhibit fever without clinical sepsis and have an absolute neutrophil count >100 cells/mm3 can be empirically treated with non-carbapenems.

Elizabethkingia meningosepticum infections with varied presentations and different antimicrobial susceptibility - A case series.

We report three sporadic infections by Elizabethkingia meningosepticum from Government Medical College Kozhikode in Kerala state, South India over a period of three years. Two cases were commenced in the community in immunocompromised children beyond the newborn period, but both recovered promptly. Another was a hospital-acquired meningitis in a newborn baby who developed neurologic sequelae. In contrast to widespread antimicrobial resistance exhibited by this pathogen, there was good susceptibility to commonly used antimicrobials such as ampicillin, cefotaxime, piperacillin, ciprofloxacin, and vancomycin. Whilst ß lactam antibiotics are found effective in the treatment of Elizabethkingia septicaemia of children, piperacillin-tazobactam, vancomycin combination seems effective empiric choice of antibiotics for neonatal meningitis due to Elizabethkingia; there is a need for guidelines for the management of this infection, especially in neonatal meningitis.

Cidofovir for Viral Infections in Immunocompromised Children: Guidance on Dosing, Safety, Efficacy, and a Review of the Literature.

To describe the use of cidofovir (CDV) for viral infections in immunocompromised children (IC) and provide guidance on dosing and supportive care. A PubMed search was conducted for literature published between 1997 and January 2022 using the following terms: cidofovir, plus children or pediatrics. Limits were set to include human subjects less than 24 years of age receiving intravenous (IV) or intrabladder CDV for treatment of infections due to adenovirus, polyomavirus-BK (BKV), herpesviruses, or cytomegalovirus. Data were heterogeneous, with largely uncontrolled studies. Conventional dosing (CDV 5 mg/kg/dose weekly) was commonly used in 60% (31/52) of studies and modified dosing (CDV 1 mg/kg/dose 3 times/week) was used in 17% (9/52) of studies, despite being off-label. Nephrotoxicity reported across studies totaled 16% (65/403 patients), which was higher for conventional dosing 29 of 196 patients (15%) than modified dosing 1 of 27 patients (4%). Saline hyperhydration and concomitant probenecid remain the cornerstones of supportive care, while some regimens omitting probenecid are emerging to target BKV. To our knowledge, this is the first comprehensive review of CDV use (indications, dosing, supportive care, response, and nephrotoxicity) in pediatric IC. Effective utilization of CDV in IC remains challenging. Further prospective studies are needed to determine the optimal CDV dosing; however, less aggressive dosing regimens such as modified thrice weekly dosing or low dosing once weekly omitting probenecid to enhance urinary penetration may be reasonable alternatives to conventional dosing in some IC.

COVID-19 in immunocompromised children: comparison of SARS-CoV-2 viral load dynamics between the first and third waves.

SARS-CoV-2 dynamics across different COVID-19 waves has been unclear in immunocompromised children. We aimed to compare the dynamics of SARS-CoV-2 RNA viral load (VL) during the first and third waves of COVID-19 in immunocompromised children. A retrospective and longitudinal cohort study was conducted in a pediatric referral hospital of Argentina. The study included 28 admitted immunocompromised children with laboratory confirmed SARS-CoV-2 infection. Thirteen acquired the infection during COVID-19 first wave (May to August 2020, group 1 (G1)) and fifteen in the third wave (January to March 2022, group 2 (G2)). RNA viral load measure and its dynamic reconstruction were performed in nasopharyngeal swabs by validated quantitative, real time RT-PCR, and linear mixed-effects model, respectively. Of the 28 children included, 54% were girls, most of them had hemato-oncological pathology (57%), and the median age was 8years (interquartile range (IQR): 3-13). The dynamic of VL was similar in both groups (P = 0.148), starting from a level of 5.34 log10 copies/mL (95% confidence interval (CI): 4.47-6.21) in G1 and 5.79 log10 copies/mL (95% CI: 4.93-6.65) in G2. Then, VL decayed with a rate of 0.059 (95% CI: 0.038-0.080) and 0.088 (95% CI: 0.058-0.118) log10 copies/mL per day since diagnosis and fell below the limit of quantification at days 51 and 39 after diagnosis in G1 and G2, respectively. Our results evidenced a longer viral RNA persistence in immunocompromised pediatric patients and no difference in VL dynamic between COVID-19 first wave-attributed to ancestral infections-and third wave-attributed to Omicron infections.

Immunocompromised Children and Young Patients Living with Pets: Gaps in Knowledge to Avoid Zoonosis

Background and Objectives. Although pets are known to be beneficial for children, they could also imply risks for immunocompromised ones. We report the prevalence of children and young patients living with pets in a cohort of immunosuppressed pediatric patients and describe risk behaviors for acquiring zoonosis and compliance with veterinary recommendations. Methods. A cross-sectional, observational study was performed in a large tertiary hospital in Madrid, including immunosuppressed patients from different regions of Spain. The participants were asked to complete an online questionnaire. Results. Two hundred and eighty-four responses were received: 62.3% solid organ transplantation (177/284), 22.8% hematopoietic stem cell transplantation (65/284), and 14.8% inborn errors of immunity (42/284). The median age was 11 years (interquartile range 5.9–15.4), and 55% were boys (156/284). Up to 45% (130/284) of the respondents lived with 201 pets (74% of them dogs and cats). Half of the patients owning dogs or cats did not comply with at least one of the recommendations regarding vaccination, deworming, feeding, and/or veterinarian recommended controls. The poorest findings were related to deworming regimens. Only 42.8% (117/273) of the participants received specific recommendations from their healthcare professionals about companion animals. However, up to 97% of the families considering acquiring a pet did so when the professional did not contraindicate it (31/32), while 72% of the families having pets got rid of their pets when they were advised against animals (8/11). Conclusions. Pet ownership is frequent among immunocompromised children. They presented risky exposures for acquiring zoonoses, and basic veterinary recommendations were not frequently followed. The opinion of professionals significantly influenced the decision to acquire pets, but less than half of the families received recommendations in this regard.

Treatment with Brivudine in Immunocompromised Pediatric Patients with Herpes Zoster

Introduction: Herpes zoster (HZ) is caused by endogenous reactivation of latent varicella-zoster virus (VZV) that persists in sensory ganglia after primary infection. The incidence and severity of HZ increase during immunosuppression. Especially, immunocompromised patients are at high risk of developing a cutaneous rash and suffering from delayed healing of lesions. Bromovinyl deoxyuridine (brivudine), one of the most potent oral inhibitors of VZV replication, is widely used in the therapy of HZ in adult patients, particularly in Europe. In this study, we investigated the efficacy of brivudine in immunocompromised children to provide an outpatient treatment option. Methods: In this retrospective study, we included 64 immunocompromised pediatric patients with a median age of 14 years. Forty-seven patients received immunosuppressive therapy as part of hematopoietic stem cell transplantation and 17 patients as part of chemotherapy. Primary diagnosis was made clinically by examining the nature and the localization of the skin lesions. Laboratory confirmation was conducted based on the detection of VZV DNA in vesicle fluid and blood samples. Brivudine was administered orally at a single dose of 2 mg/kg per day. We monitored the patients’ response for the full time of treatment and observed the time of full crusting of lesions, loss of crusts, and any adverse effects that occurred. Results: Patients received medication for 7–21 days (median: 14 days). All children responded promptly to antiviral treatment and recovered completely from their HZ infections without complications. Crusting of lesions was reached after 3–14 days (median: 6 days). Full healing of skin lesions was ascertained within 7–21 days (median: 12 days). Overall, brivudine therapy was well tolerated. No clinical side effects during or after the treatment were observed. High compliance was achieved due to the once-daily dosing regimen. All patients were treated in an outpatient manner. Conclusion: Oral brivudine was a very effective and well-tolerated therapy in immunocompromised children with HZ infection. The oral administration offers the potential for outpatient treatment of HZ in these patients.

Population Pharmacokinetics of Posaconazole in Immune-Compromised Children and Assessment of Target Attainment in Invasive Fungal Disease.

Posaconazole (PSZ) is a triazole antifungal for the management of invasive fungal disease (IFD) in adults and children. Although PSZ is available as an intravenous (IV) solution, oral suspension (OS) and delayed-release tablets (DRTs), OS is the preferred formulation for pediatric use because of potential safety concerns associated with an excipient in the IV formulation and difficulty in swallowing intact tablets by children. However, poor biopharmaceutical characteristics of the OS formulation leads to an unpredictable dose-exposure profile of PSZ in children, potentially risking therapeutic failure. The goal of this study was to characterize the population pharmacokinetics (PK) of PSZ in immunocompromised children and assess therapeutic target attainment. Serum concentrations of PSZ were collected retrospectively from records of hospitalized patients. A population PK analysis was performed in a nonlinear mixed-effects modeling framework with NONMEM (v7.4). The PK parameters were scaled to body weight, then potential covariate effects were assessed. The final PK model was used to evaluate recommended dosing schemes through simulation of target attainment (as a percentage of the population having steady-state trough concentrations above the recommended target) using Simulx (v2021R1). Repeated measurement data of 202 serum concentrations of total PSZ were acquired from 47 immunocompromised patients between 1 and 21 years of age receiving PSZ either intravenously or orally, or both. A one-compartment PK model with first-order absorption and linear elimination best fit the data. The estimated absolute bioavailability (95% confidence interval) for suspension (Fs) was 16% (8-27%), which was significantly lower than the reported tablet bioavailability (Ft) [67%]. Fs was reduced by 62% and 75% upon concomitant administration with pantoprazole (PAN) and omeprazole (OME), respectively. Famotidine resulted in a reduction of Fs by only 22%. Both fixed dosing and weight-based adaptive dosing provided adequate target attainment when PAN or OME were not coadministered with the suspension. The results of this study revealed that both fixed and weight-based adaptive dosing schemes can be appropriate for target attainment across all PSZ formulations, including suspension. Additionally, covariate analysis suggests that concomitant proton pump inhibitors should be contraindicated during PSZ suspension dosing.

COVID-19 in immunocompromised children and adolescents.

Since coronavirus disease 2019 (COVID-19) became a global pandemic, concerns have arisen regarding the risks of COVID-19 in immunocompromised children and adolescents. Here we aimed to evaluate the clinical outcomes and risks of severe COVID-19 in immunocompromised pediatric patients. Previous studies reported that most children and adolescents receiving immunosuppressive medications have clinical presentations and favorable outcomes similar to those of the general pediatric population. Treatments and access to health services should not be interrupted in these populations, and continuous monitoring of the potential impact of variant strains on the risk of immunocompromised pediatric patients is warranted.

Outcomes of immunocompromised children hospitalized for Influenza, 2010-2021, the Canadian Immunization Monitoring Program Active (IMPACT)

ObjectivesTo evaluate immunocompromising conditions and subgroups of immunocompromise as risk factors for severe outcomes among children admitted for influenza. MethodsWe performed active surveillance for laboratory-confirmed influenza hospitalizations among children ≤16 years old at the 12 Canadian Immunization Monitoring Program Active hospitals, during 2010–2021. Logistic regression analyses were used to compare outcomes between immunocompromised and non-immunocompromised children, and for different subgroups of immunocompromise. The primary outcome was intensive care unit (ICU) admission; the secondary outcomes were mechanical ventilation and death. ResultsAmong 8982 children, 892 (9.9%) were immunocompromised; these patients were older (median, 5.6 (IQR, 3.1–10.0) vs. 2.4 (1–6) years; p < 0.001) than non-immunocompromised children, had a similar frequency of comorbidities, excluding immunocompromise and/or malignancy (38% (340/892) vs. 40% (3272/8090); p 0.2), but fewer respiratory symptoms, such as respiratory distress (20% (177/892) vs. 42% (3424/8090), p < 0.001).In multivariable analyses, immunocompromise (adjusted odds ratio (aOR), 0.19; 95% CI, 0.14–0.25) and its subcategories immunodeficiency (aOR, 0.16; 95% CI, 0.10–0.23), immunosuppression (aOR, 0.17; 95% CI, 0.12–0.23), chemotherapy (aOR, 0.07; 95% CI, 0.03–0.13), and solid organ transplantation (aOR, 0.17; 95% CI, 0.06–0.37) were associated with decreased probability of ICU admission in children admitted for influenza. Immunocompromise was also associated with a decreased probability of mechanical ventilation (aOR, 0.26; 95% CI, 0.16–0.38) or death (aOR, 0.22; 95% CI, 0.03–0.72). ConclusionImmunocompromised children are overrepresented among hospitalizations for influenza, but have a decreased probability of ICU admission, mechanical ventilation, and mortality following admission. Admission bias precludes generalizability beyond the hospital setting.

The Challenge of Diagnosing Invasive Pulmonary Aspergillosis in Children: A Review of Existing and Emerging Tools.

Invasive pulmonary aspergillosis remains a major cause of morbidity and mortality for immunocompromised children, particularly for patients with acute leukaemia and those undergoing haematopoietic stem cell transplantation. Timely diagnosis, using a combination of computed tomography (CT) imaging and microbiological testing, is key to improve prognosis, yet there are inherent challenges in this process. For CT imaging, changes in children are generally less specific than those reported in adults and recent data are limited. Respiratory sampling by either bronchoalveolar lavage or lung biopsy is recommended but is not always feasible in children, and serum biomarkers, including galactomannan, have important limitations. In this review we summarise the current paediatric data on available diagnostic tests for IPA and highlight key emerging diagnostic modalities with potential for future use.

Monkeypox (Mpox) outbreak during COVID-19 pandemic-Past and the future.

Monkeypox infection (Mpox) is caused by the Orthopoxvirus (OPXV) genus of the Poxviridae family, closely resembling its more famous sibling smallpox. Recently World Health Organization (WHO), have renamed monkeypox as Mpox citing racial concerns, so we will be referring to monkeypox as Mpox. There has been a recent outbreak in May 2022 when Mpox cases were identified in all six WHO regions. On July 23, 2022, WHO declared it a public health emergency. Before the current outbreak, Mpox had been reported in people from several parts of central and west African countries; and almost all Mpox cases in people outside of Africa were linked to international travel to countries where the disease commonly occurs or through imported animals. With the waning of smallpox vaccine-induced immunity, Mpox can spread in the global population. Though the virus generally does not cause high mortality in immunocompetent individuals, however, severe disease and mortality may result if the virus spreads to immunocompromised individuals, children, elderly individuals, pregnant women, and individuals living with comorbidities such as diabetes. The current transmission was suspected to have occurred through sexual activity in 95% of the persons with infection. It was found that 98% of the persons with infection were either gay or bisexual men, with 41% suffering from HIV infection. The reasons behind this current epidemiological behavior have to be studied further to formulate a hypothesis that, is it the homosexuals who need to be more concerned or is it a global concern, and is monkeypox changing its behaviour toa sexually transmitted infection? The rash, along with associated lymphadenopathy, is a clue toward Mpox infection, but polymerase chain reaction is needed for the confirmative diagnosis. With the discovery of a vaccine, repurposed antivirals, and precautionary steps to prevent the spread of infection, it might help in the containment of the virus. In addition, what we already know about Mpox has to be re-evaluated, because most of the information gathered is from low-resource settings in Africa. The world at large and health care agencies specifically needs to galvanize a well-funded global plan and research initiatives to contain the spread of Mpox. In this article, we have attempted to make the readers aware of the biology, etiopathogenesis including the changes at the cellular level the virus is causing, the changing trends of the virus transmission, and the clinical manifestations. We have also attempted to elaborate on the potential challenges and the need for early diagnosis and containment of this Mpox outbreak. This could be achieved by effectieve use of vaccination and taking social safety measures, especially by the communities at risk.

Pediatric herpes zoster ophthalmicus: a systematic review.

While typically affecting older adults and immunocompromised individuals, herpes zoster ophthalmicus (HZO) has been reported with varying manifestations and complications in children. In this review, we evaluate reported cases of pediatric HZO in the literature and discuss the epidemiology, risk factors, clinical presentation, treatment and outcomes. A literature search on PubMed, Scopus, and Web of Science databases was performed using the terms "pediatric herpes zoster ophthalmicus" and "herpes zoster ophthalmicus children." Publications that were not specific to HZO or pediatric populations were excluded, as were publications that were not available to review or not published in the English language. Fifty-seven reports describing 130 cases of HZO or HZO-related complications were reviewed. Major risk factors for pediatric HZO included intrauterine exposure to varicella or primary varicella infection at a young age; HZO also occurred in patients who had received varicella vaccination. Both healthy and immunocompromised children were affected, with the majority of affected children being immunocompetent. The diagnosis of HZO is primarily clinical. Children appear to have good vision recovery and resolution of symptoms if they are treated promptly and if they adhere to treatment regimens, except for irreversible vision loss related to uncommon complications such as optic neuritis. HZO occurs in both healthy and immunocompromised children. Recognizing this treatable condition is essential for reducing ocular and systemic morbidity. Long-term follow-up and assessments of the impact on health in adulthood are lacking. More systematic study is needed to determine the incidence of HZO in children and appropriate diagnostic and treatment protocols for the care of pediatric patients with HZO.

Covid-19 Infection on Asthma in an Immunocompromised Child: A Rare and Unusual Case

Introduction: Autoimmune lymphoproliferative syndrome is an immune system deficiency secondary to a disorder of lymphocyte homeostasis, the diagnosis of which is based on major and minor criteria. The combination of Asthma and COVID 19 has been described in numerous studies and several information has been disseminated on the presumed risk factors for COVID-19. Among these, the idea has emerged that people with autoimmune diseases have a higher risk of infection with COVID 19. The objective of our study is to assess the severity of COVID 19 infection in a patient with underlying pathologies. Observation: We report the case of an 8-year-old patient known to be asthmatic and followed for autoimmune lymphoproliferative syndrome since the age of 6 years. The patient presented to the Pediatric Infectious Diseases Department with exacerbation of asthma due to Covid-19 infection. She presented with wheezing dyspnea associated with fever and dry cough and was found to have febrile respiratory distress with wheezing rales on auscultation and signs of respiratory struggles requiring salbutamol nebulization. The evolution was marked by the improvement of dyspnea and cough with regression of fever after a therapy combining inhaled corticosteroids, antibiotics and hydroxychloroquine. Conclusion: This case study demonstrated that the occurrence of COVID 19 in an asthmatic and immunocompromised child was benign, and highlighted the dual benefit of hydroxychloroquine on COVID infection as well as on autoimmune lymphoproliferative syndrome.

Antibiotic Resistance of Streptococcus Pneumoniae, Neisseria Meningitidis, Haemophilus Influenzae and Staphylococcus Aureus in Morocco, National Data: Meta- Analysis.

Bacterial resistance to antibiotics has a very important role because it constitutes a threat to human health, especially immunocompromised people and children, this phenomenon can lead to difficulty or even the impossibility of treating certain infections. A meta-analysis from studies in Morocco on bacteria resistant to antibiotics over the last nine years and interest of bacterial: S. pneumoniae, N. meningitidis, H. influenzae and S. aureus, also the evolution their resistance. Total 654 articles in databases (206, 162, 134, and 152 articles found in: Elsevier, PubMed, Google Scholar, and other engines, respectively). For the bacteria in which we were interested, the prevalence of resistance increases with the years. Indeed, S. pneumoniae, N. meningitidis and H. influenzae, prevalence in 2012, 2016 and 2018 was respectively around (13%, 9.7%, 5.4%), (48%, 24%, 8%) and (29%, 33%, 8%). The evolution of the resistance of S. pneumoniae, was impacted by the introduction of the vaccine, indeed, the rate of its resistance to the antibiotic erythromycin before vaccination was 76% but after the introduction of the vaccine it decreased to 61%, while the incidence of pneumonia was 17.7%, and after vaccination it decreased to 10.2%. Also, the resistance of S. pneumoniae to penicillin G increased from 2.7% in 2011 to 100% in 2020. For N. meningitidis, resistance to penicillin G increased from 11.1% to 24% between 2012 and 2019. About of H. Influenzae for Bactrim, fluoroquinolones and tetracycline (16%, 4.8%, 2.5%), S.aureus resistance increases significantly. From 2016 to 2018, the resistance of S. aureus (Penicillin G 92%, ciprofloxacin 16.5%, erythromycin 14.6%).

First Bacteremia Due to Corynebacterium gottingense in an Immunocompromised Child: A Case Report, 16S rDNA-Based Phylogenetic Analyses and Review of the Literature

Corynebacterium gottingense is a Gram-positive bacillus that has not been reported as pathogenic in pediatric patients. Herein, a case of catheter-associated bloodstream infection by C. gottingense in a 13-year-old immunocompromised child with febrile neutropenia induced for osteosarcoma is reported. The species was identified by Sanger sequencing of the 16s rRNA sequence of the bacterial strain and was compared phylogenetically with published sequences. As suggested in the literature, the presented strain was multi-susceptible, particularly to amoxicillin. The patient was treated with piperacillin/tazobactam for seven days in the context of a urinary co-infection, resulting in resolution of fever within 48 h and then relaunched with oral amoxicillin for 3 days (for a total of 10 days of antibiotic therapy). Phylogenetic analyses based on 16S rDNA demonstrated the complexity of the genus Corynebacterium spp. but failed to demonstrate a direct benefit in predicting clinical outcome based on this single information.

Barriers to vaccination in immunocompromised children: A needs assessment in children with childhood-onset SLE and inflammatory bowel disease.

Vaccination of immunocompromised children (ICC) remains suboptimal. Needs assessment surveys were administered to patients and caregivers during routine ambulatory visits to the rheumatology and gastroenterology clinics at Nationwide Children's Hospital (NCH) from January 1 through August 31, 2018, and to community primary care physicians (PCPs) at their monthly meeting and electronically. Completed surveys were received for 57 patients (31 with childhood-onset systemic lupus erythematosus (c-SLE) and 26 with inflammatory bowel disease (IBD)) and 30 PCPs. Of the patient cohort, 93% (n = 53) felt their PCP was well informed about vaccines and 84% (n = 47) received vaccinations from either their PCP or local health department. Two patient surveys noted concerns of vaccine safety. Among the 30 responses completed by PCPs 50% (n = 15) preferred to provide all vaccines themselves, however, only 40% (n = 12) of PCPs felt "very confident" when providing vaccines to ICC. Further, 83% (n = 25) did not stock the 23-valent pneumococcal vaccine and only 27% (n = 8) routinely recommended vaccination of household contacts. Our study found a discordance between parent and PCP comfort in vaccinating ICC, highlighting an important barrier to vaccination in this patient population. In our cohort of patients, vaccine hesitancy was not a barrier to vaccination.

Cytokine storm in HSCT for severe combined immunodeficiency infant with SARS-COV-2

Hematopoietic stem cell transplant (HSCT) is the only potentially curative option for severe combined immunodeficiency (SCID) as they are extremely vulnerable to infections. Immunocompromised children are at a higher risk of SARS-CoV-2 infection with prolonged virus shedding, but have a milder disease unlike adults. However, mortality risk increases with neutropenia and in the early transplant period. For these reasons, HSCT is generally deferred when a patient is infected with SARS-COV-2. This decision has to be individualized taking into account the risk of disease progression with delay in transplant. We describe a case of a SCID infant, who had multiple, life-threatening infections (methicillin-resistant Staphylococcus aureus liver abscess, Escherichia coli sepsis, and disseminated Bacillus Calmette-Guerinosis) referred for HSCT. He unfortunately developed SARS-COV-2 infection after the conditioning was commenced for haploidentical stem cell transplant. Foreseeing many challenges with COVID, the transplant was undertaken in the pediatric intensive care unit (PICU) setting. Anticipation, recognition, and timely intervention in the PICU of exaggerated posttransplant cytokine release syndrome and pancreatitis enabled a successful outcome. To the best of our knowledge, this is the youngest pediatric HSCT performed to date with active SARS-COV-2 and first in India.

The first case of Wickerhamomyces anomalus fungemia in Iran in an immuneodeficient child, a review on the literature.

The incidence of invasive candidiasis in pediatric patients is increasing and is associated with significant morbidity and mortality. C. pelliculosa has been rarely reported as a human pathogen, however, it has been associated with serious nosocomial infections and clonal outbreaks with poor clinical outcomes in immunocompromised children were reported. Here, we describe the first case of candidemia due to Candida pelliculosa in a 5-year-old immunocompromised male suffered from Griscelli syndrome with hemophagocytic syndrome hospitalized in the pediatric intensive care unit (PICU), Tehran, Iran. In addition, the history of reported cases or case-series due to C. pelliculosa is reviewed.

Impact of COVID-19 Related Restrictions on Infections in Children with Cancer or after Hematopoietic SCT.

Infections are a major concern for immunocompromised children. We investigated whether non-pharmaceutical interventions (NPIs) implemented in the general population during the coronavirus disease 2019 (COVID-19) pandemic in Germany had an impact on frequency, type and severity of infections in these patients. We analyzed all admissions to the clinic of pediatric hematology, oncology and stem cell transplantation (SCT) with (suspected) infection or fever of unknown origin (FUO) from 2018 to 2021. We compared a 27-month period before NPIs (Pre-COVID: 01/2018-03/2020; 1041 cases) with a 12-month period with underlying NPIs (COVID: 04/2020-03/2021; 420 cases). During the COVID period the number of in-patient stays with FUO or infections decreased (38,6 cases/month vs. 35,0 cases/month), the median duration of hospital stays was longer (8 d (CI95: 7-8 d) vs. 9 d (CI95: 8-10 d) P=0,02)), the mean number of antibiotics per case increased (2,1 (CI95: 2,0-2,2) vs. 2,5 (CI95: 2,3-2,7); P=0,003)) and a substantial reduction of viral respiratory and gastrointestinal infections per case was seen (0,24 vs. 0,13; P<0,001). Notably, there was no detection of respiratory syncytial virus, influenza and norovirus, between May 2020 and March 2021. Based on need of intensive care measures and further parameters we conclude that severe (bacterial) infections were not significantly reduced by NPIs. Introduction of NPIs in the general population during the COVID-pandemic substantially reduced viral respiratory and gastrointestinal infections in immunocompromised patients, while severe (bacterial) infections were not prevented.