Exogenous interleukin-2 can rescue in-vitro T cell activation and proliferation in patients with a novel capping protein regulator and myosin 1 linker 2 mutation.

Capping protein regulator and myosin 1 linker 2 (CARMIL2) deficiency is characterized by impaired T cell activation, which is attributed to defective CD28-mediated co-signaling. Herein, we aimed to analyze the effect of exogenous interleukin (IL)-2 on in-vitro T cell activation and proliferation in a family with CARMIL2 deficiency. This study included four children (one male and three females; aged 2·5-10 years at presentation). The patients presented with inflammatory bowel disease and recurrent viral infections. Genetic analysis revealed a novel homozygous 25-base pairs deletion in CARMIL2. Immunoblotting demonstrated the absence of CARMIL2 protein in all four patients and confirmed the diagnosis of CARMIL2 deficiency. T cells were activated in-vitro with the addition of IL-2 in different concentrations. CD25 and interferon (IFN)-γ levels were measured after 48 h and 5 days of activation. CD25 surface expression on activated CD8+ and CD4+ T cells was significantly diminished in all patients compared to healthy controls. Additionally, CD8+ T cells from all patients demonstrated significantly reduced IFN-γ production. When cells derived from CARMIL2-deficient patients were treated with IL-2, CD25 and IFN-γ production increased in a dose-dependent manner. T cell proliferation, as measured by Cell Trace Violet, was impaired in one patient and it was also rescued with IL-2. In conclusion, we found that IL-2 rescued T cell activation and proliferation in CARMIL2-deficient patients. Thus, IL-2 should be further studied as a potential therapeutic modality for these patients.

Measles-related hospitalizations and associated complications in Jerusalem, 2018-2019.

OBJECTIVES: The 2018 measles outbreak in Israel affected >2000 people in Jerusalem. The aim of the study was to describe clinical features and complications of hospitalized measles patients in Jerusalem, as related to age group and risk factors. METHODS: All individuals hospitalized with measles in the three main hospitals in Jerusalem during March 2018 to February 2019 were included. Demographic, clinical and laboratory data were analysed. RESULTS: Of 161 hospitalized individuals, 86 (53.4%) were <5 years old, 16 (10%) were ≥5 years but <20 years old, and 59 (36.6%) were ≥20 years old. Most, 114/135 (85%), were unvaccinated. Immunocompromised state was identified in 12/161 (7.5%) patients, 20/161 (12.4%) had other underlying co-morbidities, and four were pregnant. Hypoxaemia on admission was a common finding in all age groups. Hepatitis was more common among adults ≥20 years old (33/59, 59%). Measles-related complications were noted in 95/161 (59%) patients, and included pneumonia/pneumonitis (67/161, 41.6%), which was more common in young (<5 years) children, diarrhoea (18/161, 11.2%), otitis (18/161, 11.2%), and neurological complications (6/161, 3.7%)-the latter occurring more frequently in the 5- to 20-year age group. Two of the 12 immunocompromised patients died of measles-related complications. A high re-admission rate (19/161, 11.8%) within 3 months was documented among hospitalized measles patients. CONCLUSION: The burden of hospitalization, as well as the high rate of short- and long-term complications observed in hospitalized patients, underscore the importance of maintaining a high measles vaccine coverage, with enhanced targeting of unvaccinated population pockets.

Distribution of fluconazole-resistant Candida bloodstream isolates among hospitals and inpatient services in Israel.

The emergence of fluconazole-resistant Candida (FRC) is worrisome, but little is known about susceptibility patterns in different nosocomial settings. We prospectively analysed Candida bloodstream isolates in 18 medical centres in Israel (six tertiary-care and 12 community hospitals). The study included 444 episodes of candidaemia (450 patient-specific isolates, 8.5% fluconazole-resistant). Institutional FRC bloodstream infection rates correlated with annual inpatient days, and were strongly associated with the presence and activity of haematology/oncology services. Infection with Candida krusei and fluconazole-resistant Candida glabrata occurred exclusively in hospitals with >600 beds. These findings suggest that empirical antifungal strategies should be tailored to the nosocomial setting.

Outcome of antibiotic lock technique for persistent central venous catheter-associated coagulase-negative Staphylococcus bacteremia in children.

The purpose of this study was to assess the long-term effectiveness of the antibiotic lock technique (ALT) in conjunction with systemic antibiotics for the salvage of long-term central venous catheter (CVC)-associated coagulase-negative Staphylococcus (CONS) bloodstream infections (BSIs) in children. A retrospective study of children with CVC-associated CONS BSIs treated with systemic vancomycin and ALT with vancomycin was carried out. The primary outcome was the immediate and 3-month success rate of salvage of the CVC. During the study period, 23 patients had persistent CONS bacteremia and were treated with ALT and systemic vancomycin. Of the 23 vancomycin lock treatments, eight catheters were removed during the acute event because of persistent bacteremia, six had relapse of CONS bacteremia within 30 days, and two had relapse within 90 days. Only seven CVCs (30%) were salvaged. Long-term transcutaneous CVCs (Hickman CVCs) were significantly associated with higher salvage rates than implantable ports (75% vs. 18%, P = 0.05). ALT with vancomycin for CVC-associated bacteremia has a limited long-term effectiveness, especially with implantable ports. Larger prospective studies are needed for the long-term evaluation of this technique.

Cytomegalovirus-associated protein-losing gastropathy in childhood.

Menetrier's disease is an uncommon disease in childhood, characterized by gastric hypertrophy and hypoalbuminemia secondary to protein loss through the gastric mucosa. This paper describes a series report of protein-losing gastropathy associated with cytomegalovirus (CMV) infection in children and reviews the literature. We reviewed the medical records of eight children with diagnosis of Menetrier's disease or protein-losing gastropathy with evidence of acute CMV infection. During a five-year period there were eight children that were diagnosed with CMV-associated protein-losing gastropathy, all in one medium-sized pediatric ward in a general hospital. The mean age was 32 months and there was no gender predominance. The most common presenting symptoms were vomiting and edema. Average symptoms' duration prior to admission was 3.2 weeks and mean albumin at presentation was 1.8 g/dl (range, 1.5-2.5 g/dl; normal values, 3.5-5 g/dl). All eight children fully recovered. In conclusion, CMV infection should be suspected in every child who presents with protein-losing gastropathy. The availability of newer, rapid diagnostic techniques such as polymerase chain reaction (PCR) may facilitate diagnosis, as serology studies may be misleading. Usually, only supportive care is required, but treatment with ganciclovir may be considered for severe or prolonged cases.

Group A streptococcus bacteraemia: comparison of adults and children in a single medical centre.

Group A streptococcus (GAS) bacteraemia is often associated with soft-tissue infection, with significant morbidity and mortality. Little is known concerning the differences between adults and children with GAS bacteraemia. Records for 98 of 116 cases of GAS bacteraemia (60 adults and 38 children, aged 7 days to 96 years) occurring during a 10-year period (1993-2002) were located and reviewed. GAS bacteraemia comprised 0.6% of all bacteraemias in adults, compared to 3.3% in children (p < 0.001). The rate of adult GAS bacteraemia was two cases/1000 hospitalisations, compared to 13/1000 in children (p < 0.001). Seventy-six (78%) patients had concomitant tissue involvement, with skin or soft-tissue infection being the most common (62%). Fifty-three (88%) of 60 adults and five (13%) of 38 children had underlying conditions (p < 0.001). Twelve patients died, only one of whom was a child. Parameters associated with mortality were older age, lower temperature, hypotension, a need for surgical intervention, toxic shock syndrome, disseminated intravascular coagulation, thrombocytopenia, lymphopenia, hypocalcaemia, renal failure and acidosis (p < 0.05).