Relationship between patient understanding and timeliness of penicillin prophylaxis in rheumatic heart disease prevention programmes in American Samoa.

AIM: While mostly eradicated in developed nations, rheumatic heart disease (RHD) is still the leading cause of preventable cardiovascular disease in children. RHD and its antecedent acute rheumatic fever remain endemic in many low to middle income countries, as well as in vulnerable communities in wealthy ones. Evidence-based interventions are particularly important in resource-poor settings. We sought to determine if efforts directed at patient and family education impact degree of participation in community-based prevention measures, and with short-term disease progression. METHODS: We performed an observational, cross-sectional study of children with RHD aged 5-19 years, along with their parents, in American Samoa. A survey was administered in November 2016 to assess patient and parent knowledge of RHD. Scores were compared to percent timeliness of penicillin prophylaxis via chart review. RESULTS: We collected a total of 70 surveys of child-parent dyads with a patient mean age of 14.28 years ±2.71. An increased knowledge score was predictive of increased penicillin compliance for both children (12.70% increase in compliance per 1-unit increase in score (P = 0.0004)) and parents (10.10% increase in compliance per 1-unit increase in score (P = 0.0012)). CONCLUSIONS: A clear relationship exists between patient and parent knowledge of RHD and timeliness of penicillin prophylaxis doses. This study was the first to link patient understanding of RHD to engagement with preventative measures.

Structure and proposed mechanism of L-α-glycerophosphate oxidase from Mycoplasma pneumoniae.

UNLABELLED: The formation of H2 O2 by the FAD-dependent L-α-glycerophosphate oxidase (GlpO) is important for the pathogenesis of Streptococcus pneumoniae and Mycoplasma pneumoniae. The structurally known GlpO from Streptococcus sp. (SspGlpO) is similar to the pneumococcal protein (SpGlpO) and provides a guide for drug design against that target. However, M. pneumoniae GlpO (MpGlpO), having < 20% sequence identity with structurally known GlpOs, appears to represent a second type of GlpO that we designate as type II GlpOs. In the present study, the recombinant His-tagged MpGlpO structure is described at an approximate resolution of 2.5 Å, solved by molecular replacement using, as a search model, the Bordetella pertussis protein 3253 (Bp3253), comprising a protein of unknown function solved by structural genomics efforts. Recombinant MpGlpO is an active oxidase with a turnover number of approximately 580 min(-1), whereas Bp3253 showed no GlpO activity. No substantial differences exist between the oxidized and dithionite-reduced MpGlpO structures. Although, no liganded structures were determined, a comparison with the tartrate-bound Bp3253 structure and consideration of residue conservation patterns guided the construction of a model for L-α-glycerophosphate (Glp) recognition and turnover by MpGlpO. The predicted binding mode also appears relevant for the type I GlpOs (such as SspGlpO) despite differences in substrate recognition residues, and it implicates a histidine conserved in type I and II Glp oxidases and dehydrogenases as the catalytic acid/base. The present study provides a solid foundation for guiding further studies of the mitochondrial Glp dehydrogenases, as well as for continued studies of M. pneumoniae and S. pneumoniae glycerol metabolism and the development of novel therapeutics targeting MpGlpO and SpGlpO. DATABASE: Structural data have been deposited in the Protein Data Bank under accession numbers 4X9M (oxidized) and 4X9N (reduced).