Final Technical Report - Open Architectures, Standards and Information Systems (OASIS II) – Developing Capacity, Sharing Knowledge and Good Principles across eHealth in Africa

The OASIS II project aimed to build on aspects of the Open Architectures, Standards and Information Systems for Healthcare in Africa (OASIS) project, previously funded by IDRC through the South African Medical Research Council. The objectives of the project included over-arching, network-wide objectives and individual project objectives. In addition, OASIS II aimed to investigate a shared research purpose and combine existing methods between one existing and four new projects and partners to: 1) elaborate a network-wide OASIS II research methodology, 2) establish an open enterprise architectural framework for eHealth in developing countries and 3) create a collaborative framework for sharing new evidence regarding the impact of eHealth solutions in resource-poor settings

Technological Change in Economic Models of Environmental Policy: A Survey

This paper provides an overview of the treatment of technological change in economic models of environmental policy. Numerous economic modeling studies have confirmed the sensitivity of mid- and long-run climate change mitigation cost and benefit projections to assumptions about technology costs. In general, technical progress is considered to be a noneconomic, exogenous variable in global climate change modeling. However, there is overwhelming evidence that technological change is not an exogenous variable but to an important degree endogenous, induced by needs and pressures. Hence, some environmenteconomy models treat technological change as endogenous, responding to socio-economic variables. Three main elements in models of technological innovation are: (i) corporate investment in research and development, (ii) spillovers from R&D, and (iii) technology learning, especially learning-by-doing. The incorporation of induced technological change in different types of environmental-economic models tends to reduce the costs of environmental policy, accelerates abatement and may lead to positive spillover and negative leakage

Progression to AIDS in South Africa Is Associated with both Reverting and Compensatory Viral Mutations

We lack the understanding of why HIV-infected individuals in South Africa progress to AIDS. We hypothesised that in end-stage disease there is a shifting dynamic between T cell imposed immunity and viral immune escape, which, through both compensatory and reverting viral mutations, results in increased viral fitness, elevated plasma viral loads and disease progression. We explored how T cell responses, viral adaptation and viral fitness inter-relate in South African cohorts recruited from Bloemfontein, the Free State (n = 278) and Durban, KwaZulu-Natal (n = 775). Immune responses were measured by γ-interferon ELISPOT assays. HLA-associated viral polymorphisms were determined using phylogenetically corrected techniques, and viral replication capacity (VRC) was measured by comparing the growth rate of gag-protease recombinant viruses against recombinant NL4-3 viruses. We report that in advanced disease (CD4 counts <100 cells/µl), T cell responses narrow, with a relative decline in Gag-directed responses (p<0.0001). This is associated with preserved selection pressure at specific viral amino acids (e.g., the T242N polymorphism within the HLA-B*57/5801 restricted TW10 epitope), but with reversion at other sites (e.g., the T186S polymorphism within the HLA-B*8101 restricted TL9 epitope), most notably in Gag and suggestive of “immune relaxation”. The median VRC from patients with CD4 counts <100 cells/µl was higher than from patients with CD4 counts ≥500 cells/µl (91.15% versus 85.19%, p = 0.0004), potentially explaining the rise in viral load associated with disease progression. Mutations at HIV Gag T186S and T242N reduced VRC, however, in advanced disease only the T242N mutants demonstrated increasing VRC, and were associated with compensatory mutations (p = 0.013). These data provide novel insights into the mechanisms of HIV disease progression in South Africa. Restoration of fitness correlates with loss of viral control in late disease, with evidence for both preserved and relaxed selection pressure across the HIV genome. Interventions that maintain viral fitness costs could potentially slow progression

Implementing school malaria surveys in Kenya: towards a national surveillance system

OBJECTIVE: To design and implement surveys of malaria infection and coverage of malaria control interventions among school children in Kenya in order to contribute towards a nationwide assessment of malaria. METHODS: The country was stratified into distinct malaria transmission zones based on a malaria risk map and 480 schools were visited between October 2008 and March 2010. Surveys were conducted in two phases: an initial opportunistic phase whereby schools were selected for other research purposes; and a second phase whereby schools were purposively selected to provide adequate spatial representation across the country. Consent for participation was based on passive, opt-out consent rather than written, opt-in consent because of the routine, low-risk nature of the survey. All children were diagnosed for Plasmodium infection using rapid diagnostic tests, assessed for anaemia and were interviewed about mosquito net usage, recent history of illness, and socio-economic and household indicators. Children's responses were entered electronically in the school and data transmitted nightly to Nairobi using a mobile phone modem connection. RDT positive results were corrected by microscopy and all results were adjusted for clustering using random effect regression modelling. RESULTS: 49,975 children in 480 schools were sampled, at an estimated cost of US$ 1,116 per school. The overall prevalence of malaria and anaemia was 4.3% and 14.1%, respectively, and 19.0% of children reported using an insecticide-treated net (ITN). The prevalence of infection showed marked variation across the country, with prevalence being highest in Western and Nyanza provinces, and lowest in Central, North Eastern and Eastern provinces. Nationally, 2.3% of schools had reported ITN use >60%, and low reported ITN use was a particular problem in Western and Nyanza provinces. Few schools reported having malaria health education materials or ongoing malaria control activities. CONCLUSION: School malaria surveys provide a rapid, cheap and sustainable approach to malaria surveillance which can complement household surveys, and in Kenya, show that large areas of the country do not merit any direct school-based control, but school-based interventions, coupled with strengthened community-based strategies, are warranted in western and coastal Kenya. The results also provide detailed baseline data to inform evaluation of school-based malaria control in Kenya

CD14+ macrophages that accumulate in the colon of African AIDS patients express pro-inflammatory cytokines and are responsive to lipopolysaccharide

BACKGROUND : Intestinal macrophages are key regulators of inflammatory responses to the gut microbiome and play a central role in maintaining tissue homeostasis and epithelial integrity. However, little is known about the role of these cells in HIV infection, a disease fuelled by intestinal inflammation, a loss of epithelial barrier function and increased microbial translocation (MT). METHODS : Phenotypic and functional characterization of intestinal macrophages was performed for 23 African AIDS patients with chronic diarrhea and/or weight loss and 11 HIV-negative Africans with and without inflammatory bowel disease (IBD). AIDS patients were treated with cotrimoxazole for the prevention of opportunistic infections (OIs). Macrophage phenotype was assessed by flow cytometry and immuno-histochemistry (IHC); production of proinflammatory mediators by IHC and Qiagen PCR Arrays; in vitro secretion of cytokines by the Bio-Plex Suspension Array System. Statistical analyses were performed using Spearman’s correlation and Wilcoxon matched-pair tests. Results between groups were analyzed using the Kruskal-Wallis with Dunn’s post-test and the Mann–Whitney U tests. RESULTS : None of the study participants had evidence of enteric co-infections as assessed by stool analysis and histology. Compared to healthy HIV-negative controls, the colon of AIDS patients was highly inflamed with increased infiltration of inflammatory cells and increased mRNA expression of proinflammatory cytokine (tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IFN-γ, and IL-18), chemokines (chemokine (C-C motif) ligand (CCL)2 and chemokine (C-X-C) motif ligand (CXCL)10) and transcription factors (TNF receptor-associated factor (TRAF)6 and T-box (TXB)21). IHC revealed significant co-localization of TNF-α and IL-1β with CD68+ cells. As in IBD, HIV was associated with a marked increase in macrophages expressing innate response receptors including CD14, the co-receptor for lipopolysaccharide (LPS). The frequency of CD14+ macrophages correlated positively with plasma LPS, a marker of MT. Total unfractionated mucosal mononuclear cells (MMC) isolated from the colon of AIDS patients, but not MMC depleted of CD14+ cells, secreted increased levels of proinflammatory cytokines ex vivo in response to LPS CONCLUSIONS : Intestinal macrophages, in the absence of overt OIs, play an important role in driving persistentinflammation in HIV patients with late-stage disease and diarrhea. These results suggest intensified treatmentstrategies that target inflammatory processes in intestinal macrophages may be highly beneficial in restoringthe epithelial barrier and limiting MT in HIV-infected patients.This research and selected researchers (EC, TR, PM, SM and CS) were funded in part by a grant from the Delegation of the European Union to South Africa: “Drug Resistance Surveillance and Treatment Monitoring Network for the Public Sector HIV Antiretroviral Treatment Programme in the Free State – Sante 2007/147-790” and by a grant from the National Research Council of South Africa, Unlocking the Future 61509.http://www.biomedcentral.com/bmcinfectdisam201