Suchergebnisse

Invasive non-typhoidal Salmonella (iNTS) disease has emerged as a major public health concern. Yet, understanding of the global burden is incomplete, limited particularly by the breadth of blood culture-based surveillance systems that are able to accurately diagnose the etiology of bacteremia. The accessibility of whole genome sequencing has allowed for genetic characterization of pathogens, shedding light on its evolutionary history and sounding alerts for its future progression. iNTS disease is observed to be a particular threat in sub-Saharan Africa, with a case fatality rate greatly exceeding that of typhoid fever, and commonly affecting infants, young children and immunocompromised adults. While iNTS disease might also be a threat in Asia and Latin America, its burden is not well characterized, primarily owing to the lack of comprehensive reporting in these regions. Drug-resistant Salmonella enterica (S. enterica) serovars (e.g. Typhimurium sequence type 313 (ST313)) have emerged as a potential consequence of sustained antibiotic pressure. Genetic analyses have identified distinguished iNTS disease-causing strains that are particularly virulent in certain human host populations. Effective treatment strategies, including vaccination, are necessary; iNTS vaccines targeting the most common S. enterica serovars, Typhimurium, Enteritidis and Dublin, are currently in early developmental stages. Funding and political support is needed to promote vaccine development and implementation programs to ultimately reduce the threat of iNTS disease in high risk areas.

Cara Lynn Kim,1 Ligia Maria Cruz Espinoza,1 Kirsten S Vannice,2 Birkneh Tilahun Tadesse,1,3,4 Ellis Owusu-Dabo,5 Raphaël Rakotozandrindrainy,6 Ilesh V Jani,7 Mekonnen Teferi,8 Abdramane Bassiahi Soura,9 Octavie Lunguya,10,11 A Duncan Steele,2 Florian Marks1,6,12,13 1International Vaccine Institute, Seoul, Republic of Korea; 2Enteric and Diarrheal Diseases, Bill & Melinda Gates Foundation, Seattle, WA, USA; 3Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; 4Center for Innovative Drug Development and Therapeutic Trials for Africa, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; 5School of Public Health, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana; 6University of Antananarivo, Antananarivo, Madagascar; 7Instituto Nacional de Saúde (INS), Maputo Province, Mozambique; 8Armauer Hansen Research Institute, Addis Ababa, Ethiopia; 9Institut Supérieur des Sciences de la Population, Université Joseph Ki-Zerbo de Ouagadougou, Ouagadougou, Burkina Faso; 10Department of Microbiology, Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo; 11Department of Medical Biology, University Teaching Hospital of Kinshasa, Kinshasa, Democratic Republic of the Congo; 12Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK; 13Heidelberg Institute of Global Health, University of Heidelberg, Heidelberg, GermanyCorrespondence: Florian Marks, Tel +82-2-881-1133, Email fmarks@ivi.intAbstract: While typhoid fever has largely been eliminated in high-income regions which have developed modern water, sanitation, and hygiene facilities, it remains a significant public health burden resulting in morbidity and mortality among millions of individuals in resource-constrained settings. Prevention and control efforts are needed that integrate several high-impact interventions targeting facilities and infrastructure, including those addressing improvements in sanitation, access to safe water, and planned urbanization, together with parallel efforts directed at effective strategies for use of typhoid conjugate vaccines (TCV). The use of TCVs is a critical tool with the potential of having a rapid impact on typhoid fever disease burden; their introduction will also serve as an important strategy to combat evolving antimicrobial resistance to currently available typhoid fever treatments. Well-designed epidemiological surveillance studies play a critical role in establishing the need for, and monitoring the impact of, typhoid fever control and prevention strategies implemented by public health authorities. Here, we present a perspective based on a narrative review of the impact of typhoid fever on morbidity and mortality in sub-Saharan Africa and discuss ongoing surveillance activities and the role of vaccination in prevention and control efforts.Keywords: typhoid, burden, mortality, sub-Saharan Africa, conjugate-vaccine, antimicrobial resistance

INTRODUCTION: The objective of the Health Population Africa (HPAfrica) study is to determine health behaviour and population-based factors, including socioeconomic, ethnographic, hygiene and sanitation factors, at sites of the Severe Typhoid Fever in Africa (SETA) programme. SETA aims to investigate healthcare facility-based fever surveillance in Burkina Faso, the Democratic Republic of the Congo, Ethiopia, Ghana, Madagascar and Nigeria. Meaningful disease burden estimates require adjustment for health behaviour patterns, which are assumed to vary among a study population. METHODS AND ANALYSIS: For the minimum sample size of household interviews required, the assumptions of an infinite population, a design effect and age-stratification and sex-stratification are considered. In the absence of a population sampling frame or household list, a spatial approach will be used to generate geographic random points with an Aeronautical Reconnaissance Coverage Geographic Information System tool. Printouts of Google Earth Pro satellite imagery visualise these points. Data of interest will be assessed in different seasons by applying population-weighted stratified sampling. An Android-based application and a web service will be developed for electronic data capturing and synchronisation with the database server in real time. Sampling weights will be computed to adjust for possible differences in selection probabilities. Descriptive data analyses will be performed in order to assess baseline information of each study population and age-stratified and sex-stratified health behaviour. This will allow adjusting disease burden estimates. In addition, multivariate analyses will be applied to look into associations between health behaviour, population-based factors and the disease burden as determined in the SETA study. ETHICS AND DISSEMINATION: Ethic approvals for this protocol were obtained by the Institutional Review Board of the International Vaccine Institute (No. 2016-0003) and by all collaborating institutions of participating countries. It is anticipated to disseminate findings from this study through publication on a peer-reviewed journal.