Age is the most consistent host factor for severity of illness in rickettsial infections (50,51). In the preantibiotic era, the case fatality rate for Rocky Mountain spotted fever was 7.6% for patients younger than 16 years of age, compared with 25% for patients 16 years of age or older. The case fatality rate continues to be substantially higher in older persons currently with increased lethality in each older decade of life.
Higher case fatality rates for males that was documented for Rocky Mountain spotted fever and typhus historically has equalized between males and females infected with Rocky Mountain spotted fever in recent studies. That gender is likely to play a role is supported by higher fatalities among adult male guinea pigs infected with R. rickettsii than adult females, and a lower dose of R. conorii that kills adult male C3H/HeN mice than adult females. The basis for this difference in susceptibility/resistance is not known.
Host factors related to underlying diseases and enhanced oxidative stress also appear to determine severity of rickettsioses. Patients with diabetes mellitus have an increased risk of a fatal outcome with Mediterranean spotted fever. Anecdotal descriptions suggest that alcohol abuse and cardiovascular disease may be risk factors for severity of rickettsial illness.
Sulfonamide treatment exacerbates the severity of illness caused by rickettsial infection. It is possible that sulfonamides increase oxidative stress, a pathogenic mechanism of cell injury in R. rickettsii infection in vitro. Glucose-6-phosphate dehydrogenase deficiency is associated with the occurrence of fulminant Rocky Mountain spotted fever in African-American males and has been reported in unusually severe cases of murine typhus and Mediterranean spotted fever. Glucose-6-phosphate dehydrogenase is a component of the antioxidant protective mechanisms, and its deficiency could result in increased damage secondary to oxidative stress. Fulminant Rocky Mountain spotted fever is associated with hemolysis whether or not the patient is deficient in glucose-6-phosphate dehydrogenase. The release of iron-containing hemoglobin from erythrocytes could exacerbate the reactions involving free radicals of oxygen that are hypothesized to play a role in tissue injury in spotted fever rickettsiosis.
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