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    • Second although it is an important and biologically plausibl

    2019-06-25

    Second, although it is an important and biologically plausible refinement, risk-factor adjustment based on lack of access to improved water in rural areas and urban slums could be open to criticism, as the authors acknowledge. The imperfect relation between access to improved water and consumption of microbiologically safe water is underscored by the occurrence of massive typhoid fever outbreaks in settings with water sources that would be classified as improved. Third, reliable estimates of typhoid fever complications and death remain elusive. Hospital-based studies can be biased towards severe disease, yet the early detection and treatment of cases inherent and appropriate in high-quality populated-based disease surveillance systems undoubtedly modifies patients\' outcomes. Finally, it is important to ask how the results stack up against other sources of data. Few would question that typhoid fever has declined in a number of Asian countries. Furthermore, there have been increasing reports of high levels of endemic and epidemic typhoid fever from some locations in Africa. However, studies of community-acquired bloodstream infections suggest that non-typhoidal has been more common than typhoidal in sub-Saharan Africa and national disease surveillance data do not seem consistent with the suggestion that South Africa is a country with a high incidence of typhoid fever. Indeed, as highlighted by Mogasale and colleagues, incidence estimates for sub-Saharan Africa are heavily influenced by one population-based study from an urban slum in Nairobi, Kenya. The recently completed multicountry study of typhoid fever incidence in Africa should go some way to providing more data and addressing these concerns. Burden of disease estimates are foundational to building the investment case for both vaccine and non-vaccine interventions for typhoid fever. Decisions about who would most benefit from ck1 inhibitor and at what age rely on a clear epidemiological picture. Our picture of typhoid fever burden remains clouded, but Mogasale and colleagues have made refinements that challenge us to think more deeply and to value new data. Soon two new estimates of global typhoid and paratyphoid fever burden, from IHME GBD 2013 and the WHO Foodborne Diseases Burden Epidemiology Reference Group, will become available. The iterative process of refining and updating burden estimates for typhoid fever is now occurring both consecutively and in parallel, with multiple groups working somewhat independently. Looking to the future, it might be time to take stock of existing estimates and methods, drawing from the strengths of each approach, and striving for both methods that are transparent and results that are timely. Typhoid control would benefit from collective effort to ensure the best possible data to support policy decisions and from a clear message to the world on the scale of the problem. JAC serves as a resource adviser, Invasive infections, to the WHO Foodborne Diseases Burden Epidemiology Reference Group; an expert for the Institute for Health Metrics and Evaluation Global Burden of Disease 2013 project; and a reviewer for the Coalition against Typhoid (CaT) typhoid vaccine investment case. JAC is supported by the joint US National Institutes of Health-National Science Foundation Ecology and Evolution of Infectious Disease program (R01 TW009237) and the UK Biotechnology and Biological Sciences Research Council (BBSRC) (BB/J010367/1), and by UK BBSRC Zoonoses in Emerging Livestock Systems awards BB/L017679, BB/L018926, and BB/L018845.
    The Xpert MTB/RIF assay is an accurate test for the diagnosis of tuberculosis when an adequate sputum sample can be obtained; even in smear-negative tuberculosis the sensitivity is about 67%. Although the assay turnaround time is under 2 h, depending on the health-care setting, time to tuberculosis treatment can be 2 weeks or more in a substantial number of patients. The technology has now been endorsed by WHO as a frontline test for tuberculosis in populations where there is a high incidence of HIV. Indeed, several countries in Africa are rolling out Xpert MTB/RIF. However, for expanded and sustained uptake, governments and policy makers require information about the cost-effectiveness of the technology to allow for appropriate planning and allocation of health-care resources. Cost-effectiveness must be balanced against affordability and sustainability. Thus, although the diagnostic accuracy of the technique is not in doubt, questions remain about the cost-effectiveness of the technology given that the overall number of patients treated for tuberculosis can remain unchanged and given the high rates of empirical treatment in resource-poor health-care settings.