Estimating the Burden of Febrile Illnesses

Fever without localizing features, hereafter referred to as fever or febrile illness, is among the most common reasons for persons in low-resource areas to seek health care [1,2]. The nonspecific clinical presentation of many infections that cause fever makes it difficult to distinguish one from another based on clinical history and physical examination alone. Beyond malaria diagnostics, laboratory assays for many febrile diseases are often complex, costly, and may have limitations of sensitivity and specificity. Consequently, they are not widely available in low-resource areas where epidemiologic information on the etiology of febrile illness is sparse. Undifferentiated fever is the main clinical feature of many diseases of global importance, including malaria, invasive bacterial diseases, several bacterial zoonoses, and many viral infections [3]. The World Health Organization (WHO) Foodborne Diseases Epidemiology Reference Group (FERG) is tasked with estimating burden of disease for conditions transmitted by food [4]. The vast majority of enteric conditions transmitted by food are associated with diarrhea, a syndromic grouping or "envelope" that can in turn be broken down by diarrhea-associated pathogen. However, a number of foodborne diseases are associated with fever rather than diarrhea, and the absence of a febrile illness "envelope" requires novel approaches to burden of disease estimation. Examples of such foodborne diseases presenting predominantly as febrile illnesses include typhoid and paratyphoid fevers, invasive non-typhoidal Salmonella disease, brucellosis, and listeriosis. It is likely that food safety interventions could have a substantial impact on the global burden of febrile illness [5]. Here, we describe some of the challenges and potential solutions to estimating burden of febrile conditions, including those transmitted by contaminated food.