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Fever is one of the most common symptoms reported by patients seeking health care in low-resource areas in the tropics, where it may occur either in isolation or in association with other common symptoms such as cough or diarrhea (Feikin and others 2011; Prasad, Sharples, and others 2015). Fever without localizing features presents a particular challenge to health care workers and health systems because it may be caused by a wide range of bacterial, fungal, parasitic, and viral infections (Crump and others 2013; Mayxay and others 2013), as well as by noninfectious conditions. Clinical assessment has limited accuracy both for identifying the likely cause and for the early recognition of patients who will progress to serious or fatal disease. Compounding the limitations of clinical assessment is the dearth of available epidemiologic data on common causes of fever (Crump 2014) and absence of clinical laboratory services in many areas (Archibald and Reller 2001; Petti and others 2006). Given its prevalence and severity, malaria has been the common default diagnosis for fever without localizing features in the tropics for decades (WHO 2006). In countries historically highly endemic for malaria, fever is controlled and managed with vertical programs. However, a growing number of fever etiology studies (Prasad, Murdoch, and others 2015; Reyburn and others 2004) and more widespread use of malaria diagnostic tests (WHO 2010b) have served to unmask the problem of malaria overdiagnosis among febrile patients in many areas. Documented declines in malaria since 2004 (Murray and others 2014; WHO 2013) and expansion of nonmalarial infections such as dengue (Stanaway and others 2016), combined with widespread use of malaria diagnostic tests (WHO 2010b), mean that health care workers face a growing proportion of patients with fever and a negative malaria diagnostic test. This increase is troubling because patients presenting to hospitals with fever not due to malaria are as likely to die as those who have malaria (Reyburn and others 2004). Furthermore, vertical programs exist rarely for febrile illnesses other than malaria. This chapter identifies key challenges, issues for diagnosis and treatment of relevant infections, and data gaps for health care workers and policy makers regarding nonmalarial fever management and its cost-effectiveness. We highlight the needs for increasing etiologic research, restructuring of burden-of-disease estimates to recognize nonmalarial fever, and development of approaches to evaluating clinical interventions to improve patient outcomes.



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