Management of mIFI remains challenging in patients with CGD, but significant improvements have been made over the past decade.

Human inborn errors of IFN-γ underlie mycobacterial disease, due to insufficient IFN-γ production by lymphoid cells, impaired myeloid cell responses to this cytokine, or both. We report four patients from two unrelated kindreds with intermittent monocytosis and mycobacterial disease, including bacillus Calmette–Guérin-osis and disseminated tuberculosis, and without any known inborn error of IFN-γ. The patients are homozygous for ZNFX1 variants (p.S959* and p.E1606Rfs*10) predicted to be loss of function (pLOF). There are no subjects homozygous for pLOF variants in public databases. ZNFX1 is a conserved and broadly expressed helicase, but its biology remains largely unknown. It is thought to act as a viral double-stranded RNA sensor in mice, but these patients do not suffer from severe viral illnesses. We analyze its subcellular localization upon overexpression in A549 and HeLa cell lines and upon stimulation of THP1 and fibroblastic cell lines. We find that this cytoplasmic protein can be recruited to or even induce stress granules. The endogenous ZNFX1 protein in cell lines of the patient homozygous for the p.E1606Rfs*10 variant is truncated, whereas ZNFX1 expression is abolished in cell lines from the patients with the p.S959* variant. Lymphocyte subsets are present at normal frequencies in these patients and produce IFN-γ normally. The hematopoietic and nonhematopoietic cells of the patients tested respond normally to IFN-γ. Our results indicate that human ZNFX1 is associated with stress granules and essential for both monocyte homeostasis and protective immunity to mycobacteria.

BackgroundVaricella universal vaccination (UV) has been implemented in many countries for several years. Nevertheless, varicella UV remains debated in Europe and few data are available on the real burden of infection. We assessed the burden of varicella in Belgium through analysis of hospitalised cases during a 1-year period.MethodsData on children admitted to hospital with varicella were collected through a national network from November 2011 to October 2012. Inclusion criteria were either acute varicella or related complications up to 3 weeks after the rash.ResultsParticipation of 101 hospitals was obtained, covering 97.7% of the total paediatric beds in Belgium. 552 children were included with a median age of 2.1 years. Incidence of paediatric varicella hospitalisations reached 29.5/105 person-years, with the highest impact among those 0–4 years old (global incidence and odds of hospitalisation: 79/105 person-years and 1.6/100 varicella cases, respectively). Only 14% (79/552) of the cohort had an underlying chronic condition. 65% (357/552) of children had ≥1 complication justifying their admission, 49% were bacterial superinfections and 10% neurological disorders. Only a quarter of children (141/552) received acyclovir. Incidence of complicated hospitalised cases was 19/105 person-years. Paediatric intensive care unit admission and surgery were required in 4% and 3% of hospitalised cases, respectively. Mortality among Belgian paediatric population was 0.5/106 and fatality ratio 0.2% among our cohort.ConclusionsVaricella demonstrated a substantial burden of disease in Belgian children, especially among the youngest. Our thorough nationwide study, run in a country without varicella UV, offers data to support varicella UV in Belgium.

BackgroundIn the general population, pneumococcal polysaccharide vaccines (PPV) decrease the incidence of invasive pneumococcal disease (IPD) whereas the impact on the prevention of noninvasive pneumococcal disease is less clear. As compared with PPV, pneumococcal conjugate vaccines (PCV) provoke a higher, longer-lasting immune response resulting in a 45% decreased incidence in vaccine-type pneumonia, and a 75% decrease in vaccine-type IPD.MethodsLiterature review on pneumococcal vaccination in end-stage renal disease.ResultsAs compared with the general population, patients with chronic kidney disease (CKD) suffer increased mortality and morbidity from pneumococcal disease (PD), being up to 10-fold for those treated with dialysis. Numerous, usually small and methodological heterogeneous studies demonstrate that PPV provokes a serological response in dialysis patients, kidney transplant recipients, children with nephrotic syndrome and CKD patients receiving immunosuppressive medication. This response is of less intensity and duration than in healthy controls. Similar observations were made for the PCV. The protective value of these vaccine-elicited anti-pneumococcal antibodies in the CKD population remains to be substantiated. For patients treated with dialysis, epidemiological data demonstrate a correlation—which does not equal causality—between pneumococcal vaccination status and a slightly decreased total mortality. Clinical outcome data on the effectiveness of pneumococcal vaccination in the prevention of morbidity and mortality in the CKD population are lacking.ConclusionsAwaiting better evidence, pneumococcal vaccination should be advocated in all patients with CKD, as early in their disease course as possible. The ACIP schedule recommends a PCV-13 prime vaccination followed by a PPV-23 repeated vaccine at least 8 weeks later in pneumococcal non-vaccinated patients, and a PCV-13 vaccine at least 1 year after the latest PPV vaccine in previously vaccinated patients. In the UK, vaccination with PPV-23 only is recommended. There exist no good data supporting re-vaccination after 5 years in the dialysis population.