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Aina M.,Solina Center for International Development and Research | Igbokwe U.,Solina Center for International Development and Research | Jegede L.,Solina Center for International Development and Research | Fagge R.,Kano State Primary Health Care Management Board | And 2 more authors.
Vaccine | Year: 2017

Objective As part of its vaccine supply chain redesign efforts, Kano state now pushes vaccines directly from 6 state stores to primary health centers equipped with solar refrigerators. Our objective is to describe preliminary results from the first 20 months of Kano's direct vaccine delivery operations. Methods This is a retrospective review of Kano's direct vaccine delivery program. We analyzed trends in health facility vaccine stock levels, and examined the relationship between stock-out rates and each of cascade vaccine deliveries and timeliness of deliveries. Analysis of vaccination trends was based on administrative data from 27 sentinel health facilities. Costs for both the in-sourced and out-sourced approaches were estimated using a bottoms-up model-based approach. Results Overall stock adequacy increased from 54% in the first delivery cycle to 68% by cycle 33. Conversely, stock-out rates decreased from 41% to 10% over the same period. Similar trends were observed in the out-sourced and in-sourced programs. Stock-out rates rose incrementally with increasing number of cascade facilities, and delays in vaccine deliveries correlated strongly with stock-out rates. Recognizing that stock availability is one of many factors contributing to vaccinations, we nonetheless compared pre- and post- direct deliveries vaccinations in sentinel facilities, and found statistically significant upward trends for 4 out of 6 antigens. 1 antigen (measles) showed an upward trend that was not statistically significant. Hepatitis b vaccinations declined during the period. Overall, there appeared to be a one-year lag between commencement of direct deliveries and the increase in number of vaccinations. Weighted average cost per delivery is US$29.8 and cost per child immunized is US$0.7 per year. Conclusion Direct vaccine delivery to health facilities in Kano, through a streamlined architecture, has resulted in decreased stock-outs and improved stock adequacy. Concurrent operation of insourced and outsourced programs has enabled Kano build in-house logistics capabilities. © 2017 The Authors

Murrell B.,Stellenbosch University | Murrell B.,eHealth Africa | Murrell B.,University of Cape Town | Moola S.,Stellenbosch University | And 8 more authors.
Molecular Biology and Evolution | Year: 2013

Model-based analyses of natural selection often categorize sites into a relatively small number of site classes. Forcing each site to belong to one of these classes places unrealistic constraints on the distribution of selection parameters, which can result in misleading inference due to model misspecification. We present an approximate hierarchical Bayesian method using a Markov chain Monte Carlo (MCMC) routine that ensures robustness against model misspecification by averaging over a large number of predefined site classes. This leaves the distribution of selection parameters essentially unconstrained, and also allows sites experiencing positive and purifying selection to be identified orders of magnitude faster than by existing methods. We demonstrate that popular random effects likelihood methods can produce misleading results when sites assigned to the same site class experience different levels of positive or purifying selection-an unavoidable scenario when using a small number of site classes. Our Fast Unconstrained Bayesian AppRoximation (FUBAR) is unaffected by this problem, while achieving higher power than existing unconstrained (fixed effects likelihood) methods. The speed advantage of FUBAR allows us to analyze larger data sets than other methods: We illustrate this on a large influenza hemagglutinin data set (3,142 sequences). FUBAR is available as a batch file within the latest HyPhy distribution (, as well as on the Datamonkey web server ( © 2013 The Author.

Murrell B.,eHealth Africa | Murrell B.,Stellenbosch University | Wertheim J.O.,University of California at San Diego | Moola S.,Stellenbosch University | And 4 more authors.
PLoS Genetics | Year: 2012

The imprint of natural selection on protein coding genes is often difficult to identify because selection is frequently transient or episodic, i.e. it affects only a subset of lineages. Existing computational techniques, which are designed to identify sites subject to pervasive selection, may fail to recognize sites where selection is episodic: a large proportion of positively selected sites. We present a mixed effects model of evolution (MEME) that is capable of identifying instances of both episodic and pervasive positive selection at the level of an individual site. Using empirical and simulated data, we demonstrate the superior performance of MEME over older models under a broad range of scenarios. We find that episodic selection is widespread and conclude that the number of sites experiencing positive selection may have been vastly underestimated. © 2012 Murrell et al.

Kosakovsky Pond S.L.,University of California at San Diego | Murrell B.,Stellenbosch University | Murrell B.,eHealth Africa | Fourment M.,University of California at San Diego | And 3 more authors.
Molecular Biology and Evolution | Year: 2011

Adaptive evolution frequently occurs in episodic bursts, localized to a few sites in a gene, and to a small number of lineages in a phylogenetic tree. A popular class of "branch-site" evolutionary models provides a statistical framework to search for evidence of such episodic selection. For computational tractability, current branch-site models unrealistically assume that all branches in the tree can be partitioned a priori into two rigid classes - "foreground" branches that are allowed to undergo diversifying selective bursts and "background" branches that are negatively selected or neutral. We demonstrate that this assumption leads to unacceptably high rates of false positives or false negatives when the evolutionary process along background branches strongly deviates from modeling assumptions. To address this problem, we extend Felsenstein's pruning algorithm to allow efficient likelihood computations for models in which variation over branches (and not just sites) is described in the random effects likelihood framework. This enables us to model the process at every branch-site combination as a mixture of three Markov substitution models - our model treats the selective class of every branch at a particular site as an unobserved state that is chosen independently of that at any other branch. When benchmarked on a previously published set of simulated sequences, our method consistently matched or outperformed existing branch-site tests in terms of power and error rates. Using three empirical data sets, previously analyzed for episodic selection, we discuss how modeling assumptions can influence inference in practical situations. The Author 2011. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved.

Murrell B.,eHealth Africa | Murrell B.,Stellenbosch University | de Oliveira T.,University of KwaZulu - Natal | de Oliveira T.,University College London | And 5 more authors.
PLoS Computational Biology | Year: 2012

The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection and continuous directional selection, no evolutionary model combining these two properties has been proposed. We present two models of episodic directional selection (MEDS and EDEPS) which allow the a priori specification of lineages expected to have undergone directional selection. The models infer the sites and target residues that were likely subject to directional selection, using either codon or protein sequences. Compared to its null model of episodic diversifying selection, MEDS provides a superior fit to most sites known to be involved in drug resistance, and neither one test for episodic diversifying selection nor another for constant directional selection are able to detect as many true positives as MEDS and EDEPS while maintaining acceptable levels of false positives. This suggests that episodic directional selection is a better description of the process driving the evolution of drug resistance. © 2012 Murrell et al.

Cassol E.,MRC Unit for Inflammation and Immunity | Cassol E.,San Raffaele Scientific Institute | Cassol E.,Vita-Salute San Raffaele University | Cassol E.,Dana-Farber Cancer Institute | And 10 more authors.
Journal of Infectious Diseases | Year: 2010

Background. Microbial translocation contributes to immune activation and disease progression during chronic human immunodeficiency virus type 1 (HIV-1) infection. However, its role in the African AIDS epidemic remains controversial. Here, we investigated the relationship between markers of monocyte activation, plasma lipopolysaccharide (LPS), and HIV-1 RNA in South Africans prioritized to receive combination antiretroviral therapy (cART). Methods. Ten HIV-1-negative African controls and 80 HIV-1-infected patients with CD4 T cell counts <200 cells/mL were sampled prior to (n=60 ) or during (n=20 ) receipt of effective cART. Viral load was measurenp60 np20 d by Nuclisens; LPS by the Limulus amoebocyte lysate assay; monocyte and T cell subsets by flow cytometry; and soluble CD14, cytokines, and chemokines by enzyme-linked immunosorbent assay and customized Bio-Plex plates. Results. Three distinct sets of markers were identified. CCL2, CXCL10, and CD14+CD16+ monocyte levels were positively correlated with HIV-1 viremia. This finding, together with cART-induced normalization of these markers, suggests that their upregulation was driven by HIV-1. Plasma interleukin-6 was associated with the presence of opportunistic coinfections. Soluble CD14 and tumor necrosis factor were linked to plasma LPS levels and, as observed for LPS, remained elevated in patients receiving effective cART. Conclusions. Microbial translocation is a major force driving chronic inflammation in HIV-infected Africans receiving cART. Prevention of monocyte activation may be especially effective at enhancing therapeutic outcomes. © 2010 by the Infectious Diseases Society of America.

Eyres P.J.,Netfuse Telecom | Brown L.,Netfuse Telecom | Rohan H.,eHealth Africa
Procedia Engineering | Year: 2015

The effectiveness of both emergency services and response planning functions in humanitarian response and public health crises are significantly enhanced by the availability of location services in mobile networks. Here we describe how eHealth Africa and Netfuse Telecom are working together to use mobile network location services to improve the operational effectiveness of the 117 Ebola response call centre and support decision making and resource allocation at the National Ebola Response Centre, which is coordinating the response to the Ebola epidemic in Sierra Leone. © 2015 The Authors. Published by Elsevier Ltd.

Seebregts C.J.,eHealth Africa
Yearbook of medical informatics | Year: 2010

The overall objective of this project was to investigate ways to strengthen the OpenMRS community by (i) developing capacity and implementing a network focusing specifically on the needs of OpenMRS implementers, (ii) strengthening community-driven aspects of OpenMRS and providing a dedicated forum for implementation-specific issues, and; (iii) providing regional support for OpenMRS implementations as well as mentorship and training. The methods used included (i) face-to-face networking using meetings and workshops; (ii) online collaboration tools, peer support and mentorship programmes; (iii) capacity and community development programmes, and; (iv) community outreach programmes. The community-driven approach, combined with a few simple interventions, has been a key factor in the growth and success of the OpenMRS Implementers Network. It has contributed to implementations in at least twenty-three different countries using basic online tools; and provided mentorship and peer support through an annual meeting, workshops and an internship program. The OpenMRS Implementers Network has formed collaborations with several other open source networks and is evolving regional OpenMRS Centres of Excellence to provide localized support for OpenMRS development and implementation. These initiatives are increasing the range of functionality and sustainability of open source software in the health domain, resulting in improved adoption and enterprise-readiness. Social organization and capacity development activities are important in growing a successful community-driven open source software model.

Van Zyl H.,eHealth Africa | Dartnall L.,Sexual Violence Research Initiative
Studies in Health Technology and Informatics | Year: 2010

This paper discusses an innovative 3-step eHealth approach to translate research for target audiences' knowledge uptake in developing countries. The first step uses a knowledge transfer model for the identification and packaging of health content as well as the selection of appropriate Information and Communication Technologies (ICT) platforms; followed by consumer health informatics studies to evaluate the efficacy of addressing health consumers' information needs; and the final step recommends forming of strategic partnerships to strengthen and support knowledge transfer and sharing. The 3-step eHealth approach is based on a convergence of ICTs, and application of the practices and principles of informatics and knowledge management. It was refined during the development of AfroAIDSinfo, an AIDS information portal of the SA Medical Research Council (MRC). The approach was evaluated during the forming of a strategic partnership between the AfroAIDSinfo project of the MRC's Web and Media Technologies Platform and the Sexual Violence Research Initiative. The successful outcome of the eHealth approach served to collect evidence for good practice in informatics and knowledge management. © 2010 IMIA and SAHIA. All rights reserved.

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