Ten-year experience of more than 35,000 orofacial clefts in Africa.

BACKGROUND: Surgical correction of orofacial clefts greatly mitigates negative outcomes. However, access to reconstructive surgery is limited in developing countries. The present study reviews epidemiological data from a single charitable organization, Smile Train, with a database of surgical cases from 33 African countries from 2001-2011. METHODS: Demographic and clinical patient data were collected from questionnaires completed by the participating surgeons. These data were recorded in Excel, analyzed using SPSS and compared with previously reported data. RESULTS: Questionnaires were completed for 36,384 patients by 389 African surgeons. The distribution of clefts was: 34.44% clefts of the lip (CL), 58.87% clefts of the lip and palate (CLP), and 6.69% clefts of the palate only (CP). The male to female ratio was 1.46:1, and the unilateral: bilateral ratio 2.93:1, with left-sided predominance 1.69:1. Associated anomalies were found in 4.18% of patients. The most frequent surgeries included primary lip/nose repairs, unilateral (68.36%) and bilateral (11.84%). There was seasonal variation in the frequency of oral cleft births with the highest in January and lowest by December. The average age at surgery was 9.34 years and increased in countries with lower gross domestic products. The average hospital stay was 4.5 days. The reported complication rate was 1.92%. CONCLUSIONS: With the exception of cleft palates, results follow trends of worldwide epidemiologic reports of 25% CL, 50% CLP, and 25% CP, 2:1 unilateral:bilateral and left:right ratios, and male predominance. Fewer than expected patients, especially females, presented with isolated cleft palates, suggesting that limitations in economic resources and cultural aesthetics of the obvious lip deformity may outweigh functional concerns and access to treatment for females. A fewer than expected associated anomalies suggests either true ethnic variation, or that more severely-affected patients are not presenting for treatment. The epidemiology of orofacial clefting in Africa has been difficult to assess due to the diversity of the continent and the considerable variation among study designs. The large sample size of the data collected provides a basis for further study of the epidemiology of orofacial clefting in Africa.

Reengineering a receptor footprint of adeno-associated virus enables selective and systemic gene transfer to muscle.

Reengineering the receptor footprints of adeno-associated virus (AAV) isolates may yield variants with improved properties for clinical applications. We generated a panel of synthetic AAV2 vectors by replacing a hexapeptide sequence in a previously identified heparan sulfate receptor footprint with corresponding residues from other AAV strains. This approach yielded several chimeric capsids displaying systemic tropism after intravenous administration in mice. Of particular interest, an AAV2/AAV8 chimera designated AAV2i8 displayed an altered antigenic profile, readily traversed the blood vasculature, and selectively transduced cardiac and whole-body skeletal muscle tissues with high efficiency. Unlike other AAV serotypes, which are preferentially sequestered in the liver, AAV2i8 showed markedly reduced hepatic tropism. These features of AAV2i8 suggest that it is well suited to translational studies in gene therapy of musculoskeletal disorders.