Recruitment of Yoruba families from Nigeria for genetic research: experience from a multisite keloid study.

BACKGROUND: More involvement of sub-Saharan African countries in biomedical studies, specifically in genetic research, is needed to advance individualized medicine that will benefit non-European populations. Missing infrastructure, cultural and religious beliefs as well as lack of understanding of research benefits can pose a challenge to recruitment. Here we describe recruitment efforts for a large genetic study requiring three-generation pedigrees within the Yoruba homelands of Nigeria. The aim of the study was to identify genes responsible for keloids, a wound healing disorder. We also discuss ethical and logistical considerations that we encountered in preparation for this research endeavor. METHODS: Protocols for this bi-national intercultural study were approved by the Institutional Review Board (IRB) in the US and the ethics committees of the Nigerian institutions for consideration of cultural differences. Principles of community based participatory research were employed throughout the recruitment process. Keloid patients (patient advisors), community leaders, kings/chiefs and medical directors were engaged to assist the research teams with recruitment strategies. Community meetings, church forums, and media outlets (study flyers, radio and TV announcements) were utilized to promote the study in Nigeria. Recruitment of research participants was conducted by trained staff from the local communities. Pedigree structures were re-analyzed on a regular basis as new family members were recruited and recruitment challenges were documented. RESULTS: Total recruitment surpassed 4200 study participants over a 7-year period including 79 families with complete three-generation pedigrees. In 9 families more than 20 family members participated, however, in 5 of these families, we encountered issues with pedigree structure as members from different branches presented inconsistent family histories. These issues were due to the traditional open family structure amongst the Yoruba and by beliefs in voodoo or in juju. In addition, family members living in other parts of the country or abroad complicated timely and complete family recruitment. CONCLUSIONS: Organizational, logistics and ethics challenges can be overcome by additional administrative efforts, good communication, community involvement and education of staff members. However, recruitment challenges due to infrastructural shortcomings or cultural and religious beliefs can lead to significant delays, which may negatively affect study time lines and expectations of funding agencies.

Identification of ASAH1 as a susceptibility gene for familial keloids.

Keloids result from abnormal proliferative scar formation with scar tissue expanding beyond the margin of the original wound and are mostly found in individuals of sub-Saharan African descent. The etiology of keloids has not been resolved but previous studies suggest that keloids are a genetically heterogeneous disorder. Although possible candidate genes have been suggested by genome-wide association studies using common variants, by upregulation in keloids or their involvement in syndromes that include keloid formation, rare coding variants that contribute to susceptibility in non-syndromic keloid formation have not been previously identified. Through analysis of whole-genome data we mapped a locus to chromosome 8p23.3-p21.3 with a statistically significant maximum multipoint LOD score of 4.48. This finding was followed up using exome sequencing and led to the identification of a c.1202T>C (p.(Leu401Pro)) variant in the N-acylsphingosine amidohydrolase (ASAH1) gene that co-segregates with the keloid phenotype in a large Yoruba family. ASAH1 is an acid ceramidase known to be involved in tumor formation by controlling the ratio of ceramide and sphingosine. ASAH1 is also involved in cell proliferation and inflammation, and may affect the development of keloids via multiple mechanisms. Functional studies need to clarify the role of the ASAH1 variant in wound healing.

Prevalence of hospital-acquired enterococci infections in two primary-care hospitals in osogbo, southwestern Nigeria.

Enterococci are opportunistic bacteria that become pathogenic when they colonize niches where they are not normally found. Of recent, they have become major cause of nosocomial infections, especially of the bloodstream, urinary tract and surgical sites. The aim of this study is to determine the point-prevalence rate of human enterococci infections among hospitalized patients in Osogbo, Nigeria. The study was conducted between January and June 2009 in two primary-care hospitals in Osogbo and involved a total of 118 patients who developed clinical evidence of infection at least 48 hours after hospital admission. Appropriate clinical samples were collected from the patients after an informed consent and cultured for isolation/biochemical identification of Enterococcus species at the Bacteriology Laboratory of Ladoke Akintola University of Technology, Osogbo using standard microbiological methods. There were 525 hospital admissions within the time frame of the study of which 118 (22.5%) developed hospital acquired infection (HAI); 58 (49.2%) of which cultured positive for bacterial pathogens. Enterococci were isolated from infective focus in 7 patients, giving a prevalence rate of hospital-acquired enterococci infection of 5.9%. Two species of Enterococcus were identified; Enterococcus faecalis from urinary tract infection (UTI) and surgical site infection (SSI) of 6 (85.7%) patients and Enterococcus faecium from UTI in 1 (14.3%) patient. Other bacteria recovered from other infective foci were Klebsiella spp 31.0%, Pseudomonas spp 20.7%, Staphylococcus aureus 17.2%, Escherichia coli 12.1%, Staphylococcus epidermidis 3.4%, Streptococcus pneumoniae 1.7% and Serratia spp 1.7%. All the enterococci isolates were multiply antibiotic resistant, and 42.9% were vancomycin-resistant enterococci (VRE) with the VRE strains showing resistance to wider range of antibiotics than the vancomycin-sensitive strains. Other Gram-positive and Gram negative bacterial isolates also demonstrated multiple resistance to all commonly available antibiotics in this community except E. coli and Pseudomonas spp which were relatively sensitive to ciprofloxacin and ceftazidime. This limited study demonstrated a high prevalence rate of multiple antibiotic resistant enterococci infections among hospitalized patients in this environment. There is need for systematic surveillance of hospitals for enterococci infections; prudent use and rational prescription of antibiotics and stringent measures to reduce the prevalence rate by health education on infection control measures such as isolation, cleaning, disinfection and sterilization.

Prevalence of hospital-acquired enterococci infections in two primary-care Hospitals in Osogbo, Southwestern Nigeria

Enterococci are opportunistic bacteria that become pathogenic when they colonize niches where they are not normally found. Of recent; they have become major cause of nosocomial infections; especially of the bloodstream; urinary tract and surgical sites. The aim of this study is to determine the point-prevalence rate of human enterococci infections among hospitalized patients in Osogbo; Nigeria. The study was conducted between January and June 2009 in two primary-care hospitals in Osogbo and involved a total of 118 patients who developed clinical evidence of infection at least 48 hours after hospital admission. Appropriate clinical samples were collected from the patients after an informed consent and cultured for isolation/biochemical identification of Enterococcus species at the Bacteriology Laboratory of Ladoke Akintola University of Technology; Osogbo using standard microbiological methods. There were 525 hospital admissions within the time frame of the study of which 118 (22.5) developed hospital acquired infection (HAI); 58 (49.2) of which cultured positive for bacterial pathogens. Enterococci were isolated from infective focus in 7 patients; giving a prevalence rate of hospital-acquired enterococci infection of 5.9. Two species of Enterococcus were identified; Enterococcus faecalis from urinary tract infection (UTI) and surgical site infection (SSI) of 6 (85.7) patients and Enterococcus faecium from UTI in 1 (14.3) patient. Other bacteria recovered from other infective foci were Klebsiella spp 31.0; Pseudomonas spp 20.7; Staphylococcus aureus 17.2; Escherichia coli 12.1; Staphylococcus epidermidis 3.4; Streptococcus pneumoniae 1.7and Serratia spp 1.7. All the enterococci isolates were multiply antibiotic resistant; and 42.9were vancomycin-resistant enterococci (VRE) with the VRE strains showing resistance to wider range of antibiotics than the vancomycin-sensitive strains. Other Gram-positive and Gram negative bacterial isolates also demonstrated multiple resistance to all commonly available antibiotics in this community except E. coli and Pseudomonas spp which were relatively sensitive to ciprofloxacin and ceftazidime. This limited study demonstrated a high prevalence rate of multiple antibiotic resistant enterococci infections among hospitalized patients in this environment. There is need for systematic surveillance of hospitals for enterococci infections; prudent use and rational prescription of antibiotics and stringent measures to reduce the prevalence rate by health education on infection control measures such as isolation; cleaning; disinfection and sterilization