HHV6-Associated Hydrocephalus in a Pediatric Hematopoietic Stem Cell Transplant Recipient: An Unusual Presentation.

Human herpesvirus 6 (HHV-6) is a widely spread DNA virus that is ubiquitous and persistent with primary infection occurring in early childhood, with reactivation of the infection a common phenomenon in severely immunocompromised hosts, including hematopoietic stem cell transplant (HSCT) patients, influencing morbidity and mortality. A wide spectrum of clinical presentations is reported in the literature with HHV-6 reactivation including post-transplant limbic encephalitis (PALE). We report the unusual case of a 6-year-old female 107 days postallogenic HSCT due to transfusion dependent beta thalassemia major who developed acute cerebellitis with secondary supratentorial hydrocephalus that required invasive surgical intervention. In addition to accompanying imaging findings, the patient tested positive for HHV-6 by PCR from both serum and CSF samples and demonstrated dramatic improvement with the institution of steroid therapy in addition to ganciclovir treatment. The availability of rapid diagnostic measures in addition to a multidisciplinary approach is crucial to manage HHV-6 encephalitis and associated complications in HSCT patients.

Epidemiology and outcomes of invasive aspergillosis among pediatric immunocompromised patients: A 12-year single-center experience.

Invasive aspergillosis (IA) remains a common cause of mortality in pediatric immunocompromised populations. Much of our knowledge of IA stems from adult literature. We conducted a retrospective evaluation of cases of proven or probable IA, defined according to the 2019 EORTC/MSG criteria, in patients with underlying immunocompromising conditions at Boston Children's Hospital from January 1, 2007 to January 1, 2019. We estimated survival curves over 12 weeks using the Kaplan-Meier method for all-cause mortality, and we used univariate Cox proportional hazards modeling to evaluate for mortality risk factors. We identified 59 cases, 29% with proven and 71% with probable IA. Pulmonary IA was the most common presentation (78%). The median age at diagnosis was 11 years (range, 0.5-28). Hematopoietic cell transplantation (HCT) was the most frequent predisposing underlying condition (41%). Among affected patients, 44.8% were neutropenic and 59.3% were lymphopenic at diagnosis. The 12-week all-cause mortality rate was 25.4%; HCT recipients comprised the majority of deaths (9/15) with a hazard ratio of 2.47 [95% CI, 0.87-6.95]. No patients with congenital immunodeficiencies (n = 8) died within 12 weeks of IA diagnosis. Other risk factors that were significantly associated with mortality included mechanical ventilation at diagnosis, intensive care unit stay, and lymphopenia; treatment with an Aspergillus-active azole was associated with decreased mortality.In conclusion, our study found that in pediatric immunocompromised hosts, IA is associated with a high 12-week all-cause mortality rate, with a particular impact on the HCT population. LAY ABSTRACT: This study explores the epidemiology, outcomes and predictors of mortality of invasive aspergillosis (IA) at a high-volume pediatric center for immunocompromised hosts. Much of our understanding of pediatric IA is extrapolated from the adult literature. Our study found that IA is associated with a high 12-week all-cause mortality rate, with a particular impact on the hematopoietic cell transplantation study cohort.

Assessment of the Clinical Utility of Plasma Metagenomic Next-Generation Sequencing in a Pediatric Hospital Population.

Metagenomic next-generation sequencing (mNGS) of plasma cell-free DNA (cfDNA) is commercially available, but its role in the workup of infectious diseases is unclear. To understand the clinical utility of plasma mNGS, we retrospectively reviewed patients tested at a pediatric institution over 2 years to evaluate the clinical relevance of the organism(s) identified and the impact on antimicrobial management. We also investigated the effect of pretest antimicrobials and interpretation of molecules of microbial cfDNA per microliter (MPM) of plasma. Twenty-nine of 59 (49%) mNGS tests detected organism(s), and 28/51 (55%) organisms detected were clinically relevant. The median MPM of clinically relevant organisms was 1,533, versus 221 for irrelevant organisms (P = 0.01). mNGS test positive and negative percent agreements were 53% and 79%, respectively, and 50% of negative mNGS tests were true negatives. Fourteen percent of tests impacted clinical management by changing antimicrobial therapy. Immunocompromised status was the only patient characteristic that trended toward a significant clinical impact (P = 0.056). No patients with culture-negative endocarditis had organisms identified by mNGS. There were no significant differences in antimicrobial duration retest between tests with clinically relevant organism(s) and those that returned negative, nor were the MPMs different between pretreated and untreated organisms, suggesting that 10 days of antimicrobial therapy as observed in this cohort did not sterilize testing; however, no pretreated organisms identified resulted in a new diagnosis impacting clinical management. Plasma mNGS demonstrated higher utility for immunocompromised patients, but given the detection of many clinically irrelevant organisms (45%), cautious interpretation and infectious diseases consultation are prudent.

Mapping the Burden of Fungal Diseases in the United Arab Emirates.

The United Arab Emirates has very little data on the incidence or prevalence of fungal diseases. Using total and underlying disease risk populations and likely affected proportions, we have modelled the burden of fungal disease for the first time. The most prevalent serious fungal conditions are recurrent vulvovaginitis (~190,000 affected) and fungal asthma (~34,000 affected). Given the UAE's low prevalence of HIV, we estimate an at-risk population of 204 with respect to serious fungal infections with cryptococcal meningitis estimated at 2 cases annually, 15 cases of Pneumocystis pneumonia (PCP) annually, and 20 cases of esophageal candidiasis in the HIV population. PCP incidence in non-HIV patients is estimated at 150 cases annually. Likewise, with the same low prevalence of tuberculosis in the country, we estimate a total chronic pulmonary aspergillosis prevalence of 1002 cases. The estimated annual incidence of invasive aspergillosis is 505 patients, based on local data on rates of malignancy, solid organ transplantation, and chronic obstructive pulmonary disease (5.9 per 100,000). Based on the 2022 annual report of the UAE's national surveillance database, candidaemia annual incidence is 1090 (11.8/100,000), of which 49.2% occurs in intensive care. Fungal diseases affect ~228,695 (2.46%) of the population in the UAE.

Clinical Outcomes of COVID-19 in Newborns and Infants: A Multicenter Experience of 576 Cases.

BACKGROUND: The literature describing clinical presentation, disease course and outcomes of SARS-CoV-2 in infants remains scarce. METHODS: We conducted a retrospective study across 2 major pediatric referral centers evaluating the demographics, clinical and laboratory characteristics, management and outcomes of COVID-19 among newborns and infants in the United Arab Emirates (UAE). Clinical and biochemical markers were evaluated for their accuracy in predicting intensive care unit (ICU) transfer and death. RESULTS: A total of 576 COVID-19-positive infants were evaluated with a mean age of 164 days. The mean duration of symptoms was 1.48 days. Fever was present in 36.5% of the cohort, while 44.3% had nasal congestion. Eight infants (of 575; 1.39%) required transfer to the ICU for impending respiratory failure and 2 required invasive ventilation. Symptomatic (fever, nasal congestion) infants were not more likely to be transferred to the ICU (Chi-squared test, P = 0.77). ICU transfer was associated with a higher chance of receiving antibiotics (70.6% vs 35.4%; Chi-squared test, P = 0.003). On multivariate analysis, none of the clinical parameters (age, symptoms, laboratory tests) predicted transfer to the ICU. No deaths were reported during the observation period. CONCLUSIONS: Infants with SARS-CoV-2 infection have a benign clinical course with favorable outcomes. Less than 2% require ICU transfer. Clinical vigilance is required as none of the admission parameters predicted ICU transfer.

Emergence of highly resistant Candida auris in the United Arab Emirates: a retrospective analysis of evolving national trends.

Introduction: The Centers for Disease Prevention and Control lists Candida auris, given its global emergence, multidrug resistance, high mortality, and persistent transmissions in health care settings as one of five urgent threats. As a new threat, the need for surveillance of C. auris is critical. This is particularly important for a cosmopolitan setting and global hub such as the United Arab Emirates (UAE) where continued introduction and emergence of resistant variant strains is a major concern. Methods: The United Arab Emirates has carried out a 12 years of antimicrobial resistance surveillance (2010-2021) across the country, spanning all seven Emirates. A retrospective analysis of C. auris emergence from 2018-2021 was undertaken, utilising the demographic and microbiological data collected via a unified WHONET platform for AMR surveillance. Results: Nine hundred eight non-duplicate C. auris isolates were reported from 2018-2021. An exponential upward trend of cases was found. Most isolates were isolated from urine, blood, skin and soft tissue, and the respiratory tract. UAE nationals nationals comprised 29% (n = 186 of 632) of all patients; the remainder were from 34 other nations. Almost all isolates were from inpatient settings (89.0%, n = 809). The cases show widespread distribution across all reporting sites in the country. C. auris resistance levels remained consistently high across all classes of antifungals used. C. auris in this population remains highly resistant to azoles (fluconazole, 72.6% in 2021) and amphotericin. Echinocandin resistance has now emerged and is increasing annually. There was no statistically significant difference in mortality between Candida auris and Candida spp. (non-auris) patients (p-value: 0.8179), however Candida auris patients had a higher intensive care unit (ICU) admission rate (p-value <0.0001) and longer hospital stay (p < 0.0001) compared to Candida spp. (non-auris) patients. Conclusion: The increasing trend of C. auris detection and associated multidrug resistant phenotypes in the UAE is alarming. Continued C. auris circulation in hospitals requires enhanced infection control measures to prevent continued dissemination.

The Middle East and North Africa Diagnosis and Management Guidelines for Inborn Errors of Immunity.

Human inborn errors of immunity (IEI) are a group of 485 distinct genetic disorders affecting children and adults. Signs and symptoms of IEI are heterogeneous, and accurate diagnosis can be challenging and depends on the available human expertise and laboratory resources. The Middle East and North Africa (MENA) region has an increased prevalence of IEI because of the high rate of consanguinity with a predominance of autosomal recessive disorders. This area also exhibits more severe disease phenotypes compared with other regions, probably due to the delay in diagnosis. The MENA-IEI registry network has designed protocols and guidelines for the diagnosis and treatment of IEI, taking into consideration the variable regional expertise and resources. These guidelines are primarily meant to improve the care of patients within the region, but can also be followed in other regions with similar patient populations.

Self-esteem and other risk factors for depressive symptoms among adolescents in United Arab Emirates.

BACKGROUND: Little is known about depressive symptoms among adolescents in the United Arab Emirates (UAE). This study aimed to identify the prevalence of depression and its association with self-esteem, individual, parental and family factors among adolescents aged 12 to 18 in UAE. METHODS: Six hundred adolescents, aged 12 to 18 years were recruited from 4 of 111 schools in a cross-sectional study. We administered Beck Depression Inventory Scale and Rosenberg Self-esteem Scale to measure self-report symptoms of depression and self-esteem. We used multiple linear regression to identify significant predictors of depression. RESULTS: Over 86% of the identified sample participated to the survey. The mean age of the sample was 14.3 (±1.3) with an excess of girls (61%). Depressive symptoms were detected in 17.2% (95% CI 14.2-20.7). There was an inverse relationship between self-esteem scores and depressive symptoms. Positive predictors of depressive symptoms, having controlled for age, gender, and ethnicity included experiencing neglect, being verbally abused in school, having no monthly allowance to spend in school, a history of physical morbidities requiring treatment, being a current or past smoker and a low family income. CONCLUSION: The high prevalence of depressive symptoms measured in this survey suggests a significant public health problem among adolescents in the UAE. Public health interventions aimed at facilitating education and early detection and potential treatment of depressive symptoms are a priority in the region.