The human opportunistic pathogen Serratia marcescens is a bacterium with a broad host range, and represents a growing problem for public health. Serratia marcescens kills Caenorhabditis elegans after colonizing the nematode's intestine. We used C.elegans to screen a bank of transposon-induced S.marcescens mutants and isolated 23 clones with an attenuated virulence. Nine of the selected bacterial clones also showed a reduced virulence in an insect model of infection. Of these, three exhibited a reduced cytotoxicity in vitro, and among them one was also markedly attenuated in its virulence in a murine lung infection model. For 21 of the 23 mutants, the transposon insertion site was identified. This revealed that among the genes necessary for full in vivo virulence are those that function in lipopolysaccharide (LPS) biosynthesis, iron uptake and hemolysin production. Using this system we also identified novel conserved virulence factors required for Pseudomonas aeruginosa pathogenicity. This study extends the utility of C.elegans as an in vivo model for the study of bacterial virulence and advances the molecular understanding of S.marcescens pathogenicity.

Pernicious anemia (also known as Biermer’s disease) is an autoimmune atrophic gastritis, predominantly of the fundus, and is responsible for a deficiency in vitamin B12 (cobalamin) due to its malabsorption. Its prevalence is 0.1% in the general population and 1.9% in subjects over the age of 60 years. Pernicious anemia represents 20%–50% of the causes of vitamin B12 deficiency in adults. Given its polymorphism and broad spectrum of clinical manifestations, pernicious anemia is a great pretender. Its diagnosis must therefore be evoked and considered in the presence of neurological and hematological manifestations of undetermined origin. Biologically, it is characterized by the presence of anti-intrinsic factor antibodies. Treatment is based on the administration of parenteral vitamin B12, although other routes of administration (eg, oral) are currently under study. In the present update, these various aspects are discussed with special emphasis on data of interest to the clinician.

ObjectivesTo evaluate the prevalence of late-onset neutropenia and its complications in patients treated with rituximab (RTX) for rheumatoid arthritis (RA) and other autoimmune diseases (AIDs) in a prospective registry.MethodsThe AutoImmunity and Rituximab registry is an independent 7-year prospective registry promoted by the French Society of Rheumatology. For each episode of neutropenia, data were validated by the clinician in charge of the patient.ResultsAmong 2624 patients treated with RTX for refractory AIDs, and at least 1 follow-up visit (a total follow-up of 4179 patient-years in RA and 987 patient-years in AIDs), late-onset neutropenia was observed in 40 patients (25 RA (1.3% of patients with RA, 0.6/100 patient-years), and AIDs in 15 (2.3% of patients with AIDs, 1.5/100 patient-years)). 6 patients (15%) had neutrophils <500/mm3, 8 (20%) had neutrophils between 500 and 1000/mm3, and 26 (65%) had neutrophils between 1000 and 1500/mm3. Neutropenia occurred after a median period of 4.5 (3–6.5) months after the last RTX infusion in patients with RA, and 5 (3–6.5) months in patients with AIDs. 5 patients (12.5%), 4 of them with neutrophils lower than 500/mm3, developed a non-opportunistic serious infection and required antibiotics and granulocyte colony-stimulating factor injections, with a favourable outcome. After resolution of their RTX-related neutropenia, 19 patients (47.5%) were re-treated, and neutropenia reoccurred in 3 of them.ConclusionsLate-onset neutropenia might occur after RTX and may result in serious infections. Thus, monitoring of white cell count should be performed after RTX. However, in this large registry of patients with AIDs, the frequency of RTX-induced neutropenia was much lower than that previously reported in patients treated for blood malignancies or AIDs.