Baseline Morbidity in 2,990 Adult African Volunteers Recruited to Characterize Laboratory Reference Intervals for Future HIV Vaccine Clinical Trials

BACKGROUND: An understanding of the health of potential volunteers in Africa is essential for the safe and efficient conduct of clinical trials, particularly for trials of preventive technologies such as vaccines that enroll healthy individuals. Clinical safety laboratory values used for screening, enrolment and follow-up of African clinical trial volunteers have largely been based on values derived from industrialized countries in Europe and North America. This report describes baseline morbidity during recruitment for a multi-center, African laboratory reference intervals study. METHODS: Asymptomatic persons, aged 18-60 years, were invited to participate in a cross-sectional study at seven sites (Kigali, Rwanda; Masaka and Entebbe, Uganda; Kangemi, Kenyatta National Hospital and Kilifi, Kenya; and Lusaka, Zambia). Gender equivalency was by design. Individuals who were acutely ill, pregnant, menstruating, or had significant clinical findings were not enrolled. Each volunteer provided blood for hematology, immunology, and biochemistry parameters and urine for urinalysis. Enrolled volunteers were excluded if found to be positive for HIV, syphilis or Hepatitis B and C. Laboratory assays were conducted under Good Clinical Laboratory Practices (GCLP). RESULTS AND CONCLUSIONS: Of the 2990 volunteers who were screened, 2387 (80%) were enrolled, and 2107 (71%) were included in the analysis (52% men, 48% women). Major reasons for screening out volunteers included abnormal findings on physical examination (228/603, 38%), significant medical history (76, 13%) and inability to complete the informed consent process (73, 13%). Once enrolled, principle reasons for exclusion from analysis included detection of Hepatitis B surface antigen (106/280, 38%) and antibodies against Hepatitis C (95, 34%). This is the first large scale, multi-site study conducted to the standards of GCLP to describe African laboratory reference intervals applicable to potential volunteers in clinical trials. Approximately one-third of all potential volunteers screened were not eligible for analysis; the majority were excluded for medical reasons

Project Masihambisane: a cluster randomised controlled trial with peer mentors to improve outcomes for pregnant mothers living with HIV

Abstract Background Pregnant women living with HIV (WLH) face daily challenges maintaining their own and their babies' health and mental health. Standard Prevention of Maternal to Child Transmission (PMTCT) programs are not designed to address these challenges. Methods/Design As part of a cluster randomized controlled trial, WLH are invited to attend four antenatal and four postnatal small group sessions led by a peer WLH (a Peer Mentor). The WLH and their babies are assessed during pregnancy and at one week, six months, and twelve months post-birth. Mobile phones are used to collect routine information, complete questionnaires and remain in contact with participants over time. Pregnant WLH (N = 1200) are randomly assigned by clinic (N = 8 clinics) to an intervention program, called Masihambisane (n = 4 clinics, n = 600 WLH) or a standard care PMTCT control condition (n = 4 clinics; n = 600 WLH). Discussion Data collection with cellular phones are innovative and effective in low-resource settings. Standard PMTCT programs are not designed to address the daily challenges faced by WLH; Peer Mentors may be useful in supporting WLH to cope with these challenges. Trial registration ClinicalTrials.gov registration # NCT0097269

Recent advances in understanding hypertension development in sub-Saharan Africa

Consistent reports indicate that hypertension is a particularly common finding in black populations. Hypertension occurs at younger ages and is often more severe in terms of blood pressure levels and organ damage than in whites, resulting in a higher incidence of cardiovascular disease and mortality. This review provides an outline of recent advances in the pathophysiological understanding of blood pressure elevation and the consequences thereof in black populations in Africa. This is set against the backdrop of populations undergoing demanding and rapid demographic transition, where infection with the Human Immunodeficiency Virus predominates, and where under and over-nutrition coexist. Collectively, recent findings from Africa illustrate an increased lifetime risk to hypertension from foetal life onwards. From young ages black populations display early endothelial dysfunction, increased vascular tone and reactivity, microvascular structural adaptions, as well as increased aortic stiffness resulting in elevated central and brachial blood pressures during the day and night, when compared to whites. Together with knowledge on the contributions of sympathetic activation and abnormal renal sodium handling, these pathophysiological adaptations result in subclinical and clinical organ damage at younger ages. This overall enhanced understanding on the determinants of blood pressure elevation in blacks encourages (a) novel approaches to assess and manage hypertension in Africa better, (b) further scientific discovery to develop more effective prevention and treatment strategies, and (c) policymakers and health advocates to collectively contribute in creating health-promoting environments in Africa

Gene-Gene and Gene-Environmental Interactions of Childhood Asthma: A Multifactor Dimension Reduction Approach

Background: The importance of gene-gene and gene-environment interactions on asthma is well documented in literature, but a systematic analysis on the interaction between various genetic and environmental factors is still lacking. Methodology/Principal Findings: We conducted a population-based, case-control study comprised of seventh-grade children from 14 Taiwanese communities. A total of 235 asthmatic cases and 1,310 non-asthmatic controls were selected for DNA collection and genotyping. We examined the gene-gene and gene-environment interactions between 17 singlenucleotide polymorphisms in antioxidative, inflammatory and obesity-related genes, and childhood asthma. Environmental exposures and disease status were obtained from parental questionnaires. The model-free and non-parametrical multifactor dimensionality reduction (MDR) method was used for the analysis. A three-way gene-gene interaction was elucidated between the gene coding glutathione S-transferase P (GSTP1), the gene coding interleukin-4 receptor alpha chain (IL4Ra) and the gene coding insulin induced gene 2 (INSIG2) on the risk of lifetime asthma. The testing-balanced accuracy on asthma was 57.83 % with a cross-validation consistency of 10 out of 10. The interaction of preterm birth and indoor dampness had the highest training-balanced accuracy at 59.09%. Indoor dampness also interacted with many genes, including IL13, beta-2 adrenergic receptor (ADRB2), signal transducer and activator of transcription 6 (STAT6). We also used likelihood ratio tests for interaction and chi-square tests to validate our results and all tests showed statistical significance

Technology Assessment: Emerging Automotive Technologies for the Future

The continuous increase in human population is accompanied with more transportation demand. As a result, the pressure on transportation infrastructure has increased beyond the ability of infrastructure to catch up, leading to increased number of traffic incidents and road congestions [45, 46]. In the USA, there are more than 6 million traffic accidents, including fatality accidents that kill more than 30 thousand people every year [47]. Also, road congestion leads to a cost of about 4.8 billion hours of time, 1.9 billion gallons of wasted fuel (equivalent to 2 months operation of the Alaska Pipeline), and $101 billion in combined delay and fuel costs, aside from cost associated with travel time and dependability [17, 47, 49]