The skeletal manifestation of malaria: An epidemiological approach using documented skeletal collections.

OBJECTIVES: Recent studies in paleopathology have shown promise in associating some skeletal lesions with malarial infection. However, malaria's skeletal manifestation has never been confirmed using a large clinical reference sample from an endemic area for malaria with known individual causes of death.

MATERIALS AND METHODS: To pinpoint evidence of malaria infection on ancient skeletal remains, this study uses an epidemiological approach to compare skeletal lesions in a modern reference sample of 98 individuals from Uganda, where malaria is holoendemic, to a similar modern sample of 106 individuals from a malaria-free area.

RESULTS: Five porous skeletal lesions are identified that appear more frequently in the endemic area population, especially in anemic individuals. These appear on the cranium, vertebral column, and humeral and femoral necks. Periostitis also associates strongly with individuals in the endemic population; however, linear enamel hypoplasias show an inverse association. The identified lesions are tested for their association with each other, and then tested individually for their diagnostic power through measures of sensitivity and specificity. A diagnostic outcome algorithm is formed from the remaining skeletal lesions and their inter-lesion associations.

DISCUSSION: Several etiological explanations for the characteristic malarial skeletal lesions are explored, including severe malarial anemia, an imbalance in bone remodeling, and extramedullary erythropoiesis. The importance of careful differential diagnoses between other infectious and noninfectious causes of these lesions is discussed, including the potential for coinfection of malaria with other infectious diseases. The findings of this study are pivotal in establishing diagnostic criteria by which we can identify the prevalence and impact of malaria on past populations.