Identification by PCR of Non-typhoidal Salmonella enterica Serovars Associated with Invasive Infections among Febrile Patients in Mali

The genus Salmonella has more than 2500 serological variants (serovars), such as Salmonella enterica serovar Typhi and Salmonella Paratyphi A and B, that cause, respectively, typhoid and paratyphoid fevers (enteric fevers), and a large number of non-typhoidal Salmonella (NTS) serovars that cause gastroenteritis in healthy hosts. In young infants, the elderly and immunocompromised hosts, NTS can cause severe, fatal invasive disease. Multiple studies of pediatric patients in sub-Saharan Africa have documented the important role of NTS, in particular Salmonella Typhimurium and Salmonella Enteritidis (and to a lesser degree Salmonella Dublin), as invasive bacterial pathogens. Salmonella spp. are isolated from blood and identified by standard microbiological techniques and the serovar is ascertained by agglutination with commercial antisera. PCR-based typing techniques are becoming increasingly popular in developing countries, in part because high quality typing sera are difficult to obtain and expensive and H serotyping is technically difficult. We have developed a series of polymerase chain reactions (PCRs) to identify Salmonella Typhimurium and variants, Salmonella Enteritidis and Salmonella Dublin. We successfully identified 327 Salmonella isolates using our multiplex PCR. We also designed primers to detect Salmonella Stanleyville, a serovar found in West Africa. Another PCR generally differentiated diphasic Salmonella Typhimurium and monophasic Salmonella Typhimurium variant strains from other closely related strains. The PCRs described here will enable more laboratories in developing countries to serotype NTS that have been isolated from blood

Clinical Ethics in Gabon: The Spectrum of Clinical Ethical Issues Based on Findings from In-Depth Interviews at Three Public Hospitals

Introduction Unlike issues in biomedical research ethics, ethical challenges arising in daily clinical care in Sub-Saharan African countries have not yet been studied in a systematic manner. However this has to be seen as a distinct entity as we argue in this paper. Our aim was to give an overview of the spectrum of clinical ethical issues and to understand what influences clinical ethics in the Sub-Saharan country of Gabon. Materials and Methods In-depth interviews with 18 health care professionals were conducted at three hospital sites in Gabon. Interview transcripts were analyzed using a grounded theory approach (open and axial coding),giving a qualitative spectrum of categories for clinical ethical issues. Validity was checked at a meeting with study participants and other health care experts in Gabon after analysis of the data. Results Twelve main categories (with 28 further-specified subcategories) for clinical ethical issues were identified and grouped under three core categories: A) micro level: "confidentiality and information","interpersonal, relational and behavioral issues","psychological strain of individuals",and "scarce resources";B) meso level: "structural issues of medical institutions","issues with private clinics","challenges connected to the family",and "issues of education, training and competence";and C) macro level: "influence of society, culture, religion and superstition","applicability of western medicine","structural issues on the political level",and "legal issues". Discussion Interviewees reported a broad spectrum of clinical ethical issues that go beyond challenges related to scarce financial and human resources. Specific socio-cultural, historical and educational backgrounds also played an important role. In fact these influences are central to an understanding of clinical ethics in the studied local context. Further research in the region is necessary to put our study into perspective. As many participants reported a lack of awareness of ethical issues amongst other health care professionals in daily clinical practice, we suggest that international organizations and national medical schools should consider infrastructure and tools to improve context-sensitive capacity building in clinical ethics for Sub-Saharan African countries like Gabon

Distinct Salmonella Enteritidis lineages associated with enterocolitis in high-income settings and invasive disease in low-income settings.

An epidemiological paradox surrounds Salmonella enterica serovar Enteritidis. In high-income settings, it has been responsible for an epidemic of poultry-associated, self-limiting enterocolitis, whereas in sub-Saharan Africa it is a major cause of invasive nontyphoidal Salmonella disease, associated with high case fatality. By whole-genome sequence analysis of 675 isolates of S. Enteritidis from 45 countries, we show the existence of a global epidemic clade and two new clades of S. Enteritidis that are geographically restricted to distinct regions of Africa. The African isolates display genomic degradation, a novel prophage repertoire, and an expanded multidrug resistance plasmid. S. Enteritidis is a further example of a Salmonella serotype that displays niche plasticity, with distinct clades that enable it to become a prominent cause of gastroenteritis in association with the industrial production of eggs and of multidrug-resistant, bloodstream-invasive infection in Africa.This work was supported by the Wellcome Trust. We would like to thank the members of the Pathogen Informatics Team and the core sequencing teams at the Wellcome Trust Sanger Institute (Cambridge, UK). We are grateful to D. Harris for work in managing the sequence data

Cost effectiveness of potential ART adherence monitoring interventions in sub-saharan Africa

Background Interventions based around objective measurement of adherence to antiretroviral drugs for HIV have potential to improve adherence and to enable differentiation of care such that clinical visits are reduced in those with high adherence. It would be useful to understand the approximate upper limit of cost that could be considered for such interventions of a given effectiveness in order to be cost effective. Such information can guide whether to implement an intervention in the light of a trial showing a certain effectiveness and cost. Methods An individual-based model, calibrated to Zimbabwe, which incorporates effects of adherence and resistance to antiretroviral therapy, was used to model the potential impact of adherence monitoring-based interventions on viral suppression, death rates, disability adjusted life years and costs. Potential component effects of the intervention were: enhanced average adherence when on ART, reduced risk of ART discontinuation, and reduced risk of resistance acquisition. We considered a situation in which viral load monitoring is not available and one in which it is. In the former case, it was assumed that care would be differentiated based on the adherence level, with fewer clinic visits in those demonstrated to have high adherence. In the latter case, care was assumed to be primarily differentiated according to viral load level. The maximum intervention cost required to be cost effective was calculated based on a cost effectiveness threshold of $500 per DALY averted. Findings In the absence of viral load monitoring, an adherence monitoring-based intervention which results in a durable 6$50 per person-year on ART, mainly driven by the cost savings of differentiation of care. In the presence of viral load monitoring availability, an intervention with a similar effect on viral load suppression was cost-effective when costing $23-$32 per year, depending on whether the adherence intervention is used to reduce the level of need for viral load measurement. Conclusion The cost thresholds identified suggest that there is clear scope for adherence monitoringbased interventions to provide net population health gain, with potential cost-effective use in situations where viral load monitoring is or is not available. Our results guide the implementation of future adherence monitoring interventions found in randomized trials to have health benefit

Comparative Proteomics of Activated THP-1 Cells Infected with Mycobacterium tuberculosis Identifies Putative Clearance Biomarkers for Tuberculosis Treatment.

CAPRISA, 2015.Abstract available in pdf