The clinical presentation of a number of bacterial (e.g., leprosy 1 ) and parasitic diseases (e.g., leishmaniasis2 ), manifest across a broad clinical spectrum defined by the host immune response to infection. The poles of this spectrum are defined by either an excessive or a deficient inflammatory response to the infecting pathogen. Appropriate management of affected individuals varies according to the patient's position along this clinical and immunological continuum.Of the estimated one million deaths from malaria each year, most are attributable to severe malaria caused by Plasmodium falciparum infection. 3 Severe malaria has been increasingly recognized to be a multi-system disorder with a broad spectrum of clinical manifestations that include overlapping, evolving, or complex presentations of disease. 4 Severe malaria primarily occurs in non-immune individuals where host defense is dependent, at least partly, on innate immune responses to infection. 5 We propose that malaria may also present along a "clinicalimmunological" spectrum with differential host innate immune responses to infection, resulting in divergent clinical outcomes. 6,7 Individuals with an early deficient inflammatory response that fails to clear infection, define one pole of this spectrum. Whereas "hyper-responsive" hosts generate excess inflammation and cellular activation, which can ultimately contribute to the cerebral complications associated with cerebral malaria (CM), 8 define the opposite pole. 6 Representing the mid-range of immunological response are those with regulated responses sufficient to control parasite replication without invoking immunopathological tissue injury. In actual human infection, individuals may have complex responses and resultant mixed clinical syndromes. However, we propose a conceptual framework by which the clinical spectrum may be extended to murine models. Plasmodium berghei ANKA (PbA), a model of cerebral malaria where inflammation exacerbates disease 9, 10 and Plasmodium chabaudi chabaudi AS (PccAS), a model of malaria infection where pro-inflammatory responses are required for parasite clearance and survival 11, 12 represent the framework's divergent poles, which correspond to differing host inflammatory responses to infection.The PbA infection of susceptible mice (e.g., C57BL/6) is characterized by excessive early inflammation associated with high levels of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)/lymphotoxin-α and interferon-γ (IFN-γ), 13,14 contributing to host immunopathology and death within 6-10 days of infection caused by cerebral complications. 15 The PccAS infection is commonly used as a murine malaria model of blood stage parasite replication without cerebral complications.5 Susceptible mice lack strong proinflammatory responses, resulting in higher parasite loads and ultimately death. 16 Resistant mice show symptoms of disease, usually peaking 10-12 days post-infection, but survive through a controlled inflammatory response. 17 As such, strong inflammatory immune res...