Neutralization of the infectivity of sporozoites of Plasmodium knowlesi by antibodies to a synthetic peptide

Antibodies against a synthetic peptide representing the repetitive epitope of the circumsporozoite protein (CS) of Plasmodium knowlesi have properties similar to those of antibodies against the native protein. Either antibody reacts with the synthetic peptide, cross-links the CS protein on the membrane of the parasite giving the CSP reaction, and neutralizes the infectivity of sporozoites. The synthetic peptide and sporozoite extracts were equally effective when used in an immunoradiometric assay as antigens to detect antibodies to CS proteins. It is likely that the corresponding synthetic repeats from the human malaria parasites could be used to measure levels of anti- sporozoite antibodies in endemic areas, or to evaluate the humoral response to anti-sporozoite vaccines. The authors are grateful to Dr. Robert Gwadz, NIH, for supplying Anopheles mosquitoes and P. knowlesi sporozoites used in this study.     

Association between anti-tumour necrosis factor therapy and risk of ischaemic stroke in patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Registers-Rheumatoid Arthritis (BSRBR-RA)

BackgroundPeople with rheumatoid arthritis are at increased risk of cardiovascular morbidity and mortality, including stroke (cerebrovascular accident [CVA]). Anti-tumour necrosis factor (anti-TNF) therapy may influence the risk of CVA by reducing inflammation. The aim of the analysis was to study the association of anti-TNF therapy with risk of ischaemic CVA in rheumatoid arthritis.MethodsThe British Society for Rheumatology Biologics Registers-Rheumatoid Arthritis (BSRBR-RA) is an ongoing national prospective observational cohort study. Patients with rheumatoid arthritis recently started on anti-TNF therapy and a biologic-naive comparator group treated only with non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) were recruited to the BSRBR-RA from 2001 to 2008. Patients were followed by physician and patient questionnaires and also linked to the national death register. Incident CVAs were identified from all three sources of follow-up. CVAs were validated against WHO criteria for CVA and further classified as ischaemic CVA using CT brain reports or if ischaemic CVA was reported as the underlying cause of death from death certificates according to International Classification of Diseases 10 (ICD-10) code I63. Patients with a previous CVA were excluded. Risk of ischaemic CVA was compared between the nbDMARD cohort and people ever exposed to anti-TNF using a Cox regression model. Missing baseline data were replaced by multiple imputation. Adjustment was made for confounders using propensity scores stratified by deciles.FindingsTo Oct 31, 2010, 130 verified incident ischaemic CVAs (21 in 3271 nbDMARD patients, 109 in 11 642 anti-TNF patients) had occurred during 11 973 and 61 226 person-years of observation, respectively (incidence rate 175 vs 178 per 100 000 person-years). After adjustment for confounders, there was no association between ever exposure to anti-TNF and ischaemic CVA risk (hazard ratio 0·88 [95% CI 0·46–1·71]).InterpretationExposure to anti-TNF therapy does not appear to be associated with risk of ischaemic CVA when compared with nbDMARD therapy. Further follow-up is needed to assess time-varying risk.FundingBritish Society for Rheumatology.     

Endovascular mechanical thrombectomy for the treatment of acute ischemic stroke due to arterial dissection

Arterial dissections account for 2% of strokes in all age groups, and up to 25% in patients aged 45 years or younger. The safety of endovascular intervention in this patient population is not well characterized. We identified all patients in the Merci registry - a prospective, multi-center post-market database enrolling patients treated with the Merci Retriever thrombectomy device - with arterial dissection as the most likely stroke etiology. Stroke presentation and procedural details were obtained prospectively; data regarding procedural complications, intracerebral hemorrhage (ICH), and the use of stenting of the dissected artery were obtained retrospectively. Of 980 patients in the registry, ten were identified with arterial dissection (8/10 ICA; 2/10 vertebrobasilar). The median age was 48 years with a baseline NIH stroke scale score of 16 and median time to treatment of 4.9 h. The procedure resulted in thrombolysis in cerebral ischemia (TICI) scores of 2a or better in eight out of ten and TICI 2b or better in six out of ten patients. Stenting of the dissection was performed in four of nine (44%). The single complication (1/9; 11%) - extension of a dissected carotid artery - was treated effectively with stenting. No symptomatic ICH or stroke in a previously unaffected territory occurred. A favorable functional outcome was observed in eight out of ten patients. Despite severe strokes on presentation, high rates of recanalization (8/10) and favorable functional outcomes (8/10) were observed. These results suggest that mechanical thrombectomy in patients with acute stroke resulting from arterial dissection is feasible, safe, and may be associated with favorable functional outcomes.