Chronic Disseminated Candidiasis in Children and the Role of Corticosteroids Therapy.

BACKGROUND: Little is known about chronic disseminated candidiasis (CDC) in children. This study was done to describe the epidemiology, risk factors and outcome of CDC in children managed at Sultan Qaboos University Hospital (SQUH), Oman, and to describe the role of corticosteroids in the management of immune reconstitution inflammatory syndrome (IRIS) complicating CDC. METHODS: We retrospectively reported demographic, clinical and laboratory data of all children managed in our center for CDC between January 2013 and December 2021. In addition, we discuss the available literature on the role of corticosteroids for management of CDC-related IRIS in children since 2005. RESULTS: Between January 2013 and December 2021, 36 immunocompromised children were diagnosed with invasive fungal infection at our center, of whom 6 had CDC (all with acute leukemia). Their median age was 5.75 years. Prolonged fever despite broad-spectrum antibiotics (6/6) followed by skin rash (4/6) were the most common clinical features of CDC. Four children grew Candida tropicalis from blood or skin. CDC-related IRIS was documented in 5 children (83%) and 2 received corticosteroids. Our literature review revealed that 28 children were managed with corticosteroids for CDC-related IRIS since 2005. The majority of these children had defervescence of fever within 48 hours. Prednisolone of 1-2 mg/kg/day for 2-6 weeks was the most common regimen used. No major side effects reported in these patients. CONCLUSION: CDC is more common in children with acute leukemia and CDC-related IRIS is not uncommon. Corticosteroid therapy looks effective and safe as adjunctive therapy for CDC-related IRIS.

SARS-CoV-2-related Multisystem Inflammatory Syndrome in Children: A case series.

On 27 April 2020, the National Health Service England issued an emergency alert for a new condition owing to the observation of an increasing number of cases of a COVID-19-related hyperinflammatory syndrome termed multisystem inflammatory syndrome in children (MIS-C). Some of the presenting symptoms appeared similar to the Kawasaki disease and toxic shock syndrome. We report the cases of six children fitting the criteria of MIS-C, admitted to Royal Hospital and Sohar Hospital, Oman, between the months of June and July in 2020. Four of these patients required admission at the paediatric intensive care unit for inotropic support while two were admitted to the paediatric ward on suspicion of appendicitis. MIS-C has been reported in a small number of individuals below the age of 21 years with a median age of 9-10 years. Five of the current patients were aged less than the median age reported in the existing literature. All of the patients showed complete recovery with supportive management, intravenous immunoglobulin and steroids, with one patient requiring interleukin-6 inhibitor (tocilizumab).

Countries with similar COVID-19 vaccination rates yet divergent outcomes: are all vaccines created equal?

The world is currently engaged in a race of vaccination versus infection in an effort to control the COVID-19 pandemic. Some countries have already achieved high vaccination rates, offering a glimpse into the so-called "post-vaccination" world. We describe here a striking comparison between the similar-sized and neighboring countries of Bahrain and Qatar. While both countries have achieved impressive vaccination rates, cases increased to unprecedented levels in one country while decreasing steadily in the other. Although this could be attributed to a number of factors, we argue here that the heavy reliance on alum-adjuvanted inactivated virus vaccines may have contributed to these discrepant outcomes. We then expand the analysis to compare the outcomes of the top 10 vaccinated countries based on their reliance on inactivated virus vaccines. The results remarkably align with the initial findings seen in Bahrain and Qatar. Countries that did not use inactivated virus vaccines achieved steady declines in daily COVID-19 deaths, while other countries did not. This work highlights the urgent need to further study the effectiveness of alum-adjuvanted inactivated virus vaccines for COVID-19 before expanding their use.

Epidemiology, characteristics and outcome of children hospitalized with COVID-19 in Oman: A multicenter cohort study.

OBJECTIVES: To describe the epidemiology, clinical and laboratory features, and outcome of children hospitalized with coronavirus disease 2019 (COVID-19) in the Middle East. METHODS: A multicenter retrospective study of children hospitalized with COVID-19 in 7 centers across Oman between February and July 2020. RESULTS: In total, 56 children <14 years old required hospitalization in 7 Omani centers over 5 months (February - July 2020). Thirty-seven (68%) children were admitted with uncomplicated COVID-19, 13 (23%) with pneumonia and 5 (9%) with multisystem inflammatory syndrome in children. Infants constituted 41% of cases (23/56), approximately half of whom (12/23, 52%) were <2-months old. Fever was the most common symptom (46, 82%), followed by respiratory symptoms (33, 59%), and gastrointestinal symptoms (31, 55%). Twenty-two (39%) children had underlying medical conditions: sickle cell disease (7, 13%), chronic respiratory disease (4, 7%) and severe neurological impairment (4, 7%). Leukocytosis, elevated inflammatory markers and anemia were independently associated with intensive care admission. There were no mortalities related to admission with COVID-19 in this cohort. CONCLUSION: Most of the children hospitalized with COVID-19 had a mild course and a satisfactory outcome. Sickle cell disease is the most common comorbidity associated with pediatric admission of COVID-19 in Oman.

A digenic human immunodeficiency characterized by IFNAR1 and IFNGR2 mutations.

Primary immunodeficiencies are often monogenic disorders characterized by vulnerability to specific infectious pathogens. Here, we performed whole-exome sequencing of a patient with disseminated Mycobacterium abscessus, Streptococcus viridians bacteremia, and cytomegalovirus (CMV) viremia and identified mutations in 2 genes that regulate distinct IFN pathways. The patient had a homozygous frameshift deletion in IFNGR2, which encodes the signal transducing chain of the IFN-γ receptor, that resulted in minimal protein expression and abolished downstream signaling. The patient also harbored a homozygous deletion in IFNAR1 (IFNAR1*557Gluext*46), which encodes the IFN-α receptor signaling subunit. The IFNAR1*557Gluext*46 resulted in replacement of the stop codon with 46 additional codons at the C-terminus. The level of IFNAR1*557Gluext*46 mutant protein expressed in patient fibroblasts was comparable to levels of WT IFNAR1 in control fibroblasts. IFN-α-induced signaling was impaired in the patient fibroblasts, as evidenced by decreased STAT1/STAT2 phosphorylation, nuclear translocation of STAT1, and expression of IFN-α-stimulated genes critical for CMV immunity. Pretreatment with IFN-α failed to suppress CMV protein expression in patient fibroblasts, whereas expression of WT IFNAR1 restored IFN-α-mediated suppression of CMV. This study identifies a human IFNAR1 mutation and describes a digenic immunodeficiency specific to type I and type II IFNs.

Bacillus Calmette-Guérin vaccine related lymphadenitis in children: Management guidelines endorsed by the Saudi Pediatric Infectious Diseases Society (SPIDS).

The Bacillus Calmette-Guérin (BCG) vaccine contains live attenuated Mycobacterium bovis; was first used in humans to prevent tuberculosis (TB) in 1921. The World Health Organization (WHO) established the Expanded Program on Immunization in 1974 to ensure that all children have access to routinely recommended vaccines including BCG. Each year 120 million doses of BCG vaccine are administered worldwide. Intradermal BCG vaccine gives rise to a classic primary complex that consists of a cutaneous nodule at the site of injection and subclinical involvement of the regional lymph nodes, which is self-limiting and requires no treatment. However, ipsilateral regional lymph node enlargement may follow BCG vaccine and is considered as the most common complication, some progress to suppuration. Rarely a disseminated BCG infection may develop in immunocompromised individuals resulting in a devastating outcome. Within the last decades, variable strategies have been applied in treating lymphadenitis related to BCG vaccine, ranging from observation, anti-mycobacterial therapy, aspiration, incision and drainage to lymph node surgical excision. We are presenting these guidelines that intended to optimize and standardize management of various types of BCG related lymph adenitis in children. They are based upon the best available evidence in literature beside our experience in this field.