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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

The World Health Organization's 2035 vision is to reduce tuberculosis (TB) associated mortality by 95%. While low-burden, well-equipped industrialised economies can expect to see this goal achieved, it is challenging in the low- and middle-income countries that bear the highest burden of TB. Inadequate diagnosis leads to inappropriate treatment and poor clinical outcomes. The roll-out of the Xpert® MTB/RIF assay has demonstrated that molecular diagnostics can produce rapid diagnosis and treatment initiation. Strong molecular services are still limited to regional or national centres. The delay in implementation is due partly to resources, and partly to the suggestion that such techniques are too challenging for widespread implementation. We have successfully implemented a molecular tool for rapid monitoring of patient treatment response to anti-tuberculosis treatment in three high TB burden countries in Africa. We discuss here the challenges facing TB diagnosis and treatment monitoring, and draw from our experience in establishing molecular treatment monitoring platforms to provide practical insights into successful optimisation of molecular diagnostic capacity in resource-constrained, high TB burden settings. We recommend a holistic health system-wide approach for molecular diagnostic capacity development, addressing human resource training, institutional capacity development, streamlined procurement systems, and engagement with the public, policy makers and implementers of TB control programmes. Postprint