Children with cerebral malaria or severe malarial anaemia lack immunity to distinct variant surface antigen subsets

Abstract Variant surface antigens (VSAs) play a critical role in severe malaria pathogenesis. Defining gaps, or “lacunae”, in immunity to these Plasmodium falciparum antigens in children with severe malaria would improve our understanding of vulnerability to severe malaria and how protective immunity develops. Using a protein microarray with 179 antigen variants from three VSA families as well as more than 300 variants of three other blood stage P. falciparum antigens, reactivity was measured in sera from Malian children with cerebral malaria or severe malarial anaemia and age-matched controls. Sera from children with severe malaria recognized fewer extracellular PfEMP1 fragments and were less reactive to specific fragments compared to controls. Following recovery from severe malaria, convalescent sera had increased reactivity to certain non-CD36 binding PfEMP1s, but not other malaria antigens. Sera from children with severe malarial anaemia reacted to fewer VSAs than did sera from children with cerebral malaria, and both of these groups had lacunae in their seroreactivity profiles in common with children who had both cerebral malaria and severe malarial anaemia. This microarray-based approach may identify a subset of VSAs that could inform the development of a vaccine to prevent severe disease or a diagnostic test to predict at-risk children

Statin Use and Self-Reported Hindering Muscle Complaints in Older Persons: A Population Based Study

Statins are widely used by older persons in primary and secondary prevention of cardiovascular disease. Although serious adverse events are rare, many statin users report mild muscle pain and/or muscle weakness. It's unclear what impact statins exert on a patient's daily life. Research on statin related side effects in older persons is relatively scarce. We therefore investigated the relation between statin use and self-reported hindering muscle complaints in older persons in the general population.The present research was performed within the Integrated Systematic Care for Older Persons (ISCOPE) study in the Netherlands (Netherlands trial register, NTR1946). All registered adults aged ≥ 75 years from 59 participating practices (n = 12,066) were targeted. Information about the medical history and statin use at baseline and after 9 months was available for 4355 participants from the Electronic Patient Records of the general practitioners. In the screening questionnaire at baseline we asked participants: 'At the moment, which health complaints limit you the most in your day-to-day life?' Answers indicating muscle or musculoskeletal complaints were coded as such. No specific questions about muscle complaints were asked.The participants had a median age of 80.3 (IQR 77.6-84.4) years, 60.8% were female and 28.5% had a history of CVD. At baseline 29% used a statin. At follow-up, no difference was found in the prevalence of self-reported hindering muscle complaints in statin users compared to non-statin users (3.3% vs. 2.5%, OR 1.39, 95% CI 0.94-2.05; P = 0.98). Discontinuation of statin use during follow-up was independent of self-reported hindering muscle complaints.Based on the present findings, prevalent statin use in this community-dwelling older population is not associated with self-reported hindering muscle complaints; however, the results might be different for incident users