The Skeletal Manifestation

of Malaria

A Clinical Case-Control Study

Nicole E. Smith, Dept. of Anthropology, University of Arkansas

Identifying Malaria in the Past

aDNA and antigen detection

Cribra orbitalia and/or porotic hyperostosis

association

Other lesions? Postcranial?

Identifying Malaria in the Past

• Etiology and scope of malaria’s skeletal

manifestation is poorly understood

• Clinical comparison needed → present study

Epidemiological Approach

• Case-control study:

• Endemic and non-endemic sample populations

• Lesion association testing

• Diagnostic power testing

• Sensitivity and Specificity

• Diagnostic outcome algorithm

Illustration: Alexander Bertram Powell

Endemic Sample

• 98 skeletons: known age, sex, tribe, cause of death

• Holoendemic area for malaria

Democratic Republic of

Congo (DRC)

Tanzania

Uganda

Rwanda

BurundiMaleFemale

RwandaUgandaBurundiTanzaniaDRC

Age0-15

16-25

26-35

36-45

46-55

56+

Endemic Sample

Phases of data collection:

• Phase I: Malarial/anemic sample

• Phase II: Matched sample to Phase I

• Phase III: All remaining with skulls present

I

II

III

Non-Endemic Sample

• 352 skeletons from LSU’s FACES lab collection

• Used 106 individuals of African-American

descent – similar rates of sickle cell

• Includes cases from 1980-2013

MaleFemale

Age0-15

16-25

26-35

36-45

46-55

56+

Anemic vs. Non-Anemic Samples

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Cribra

orbitalia

Porotic

hyperostosis

Humeral

cribra

Femoral

cribra

Spinal

porosity

Periostitis Alveolar

resorption

LEHs

Non-anemic

Anemic

Humeral Cribra

Femoral Cribra

Spinal Porosity

Lesion Co-Occurrence

Cribra orbitalia

Cribra orbitalia Porotic hyperostosis

Porotic hyperostosis ☻ Humeral cribra

Humeral cribra Femoral cribra

Femoral cribra ☻ Spinal porosity

Spinal porosity Periostitis

Periostitis ☻ ☻Alveolar

resorption

Alveolar resorption LEH

LEH

Endemic vs. Non-endemic Samples

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Cribra

orbitalia

Porotic

hyperostosis

Humeral

cribra

Femoral

cribra

Spinal

porosity

Periostitis Alveolar

resorption

LEHs

Non-endemic

Endemic

Diagnostic Testing

Endemicity (Gold Standard)

Endemic Non-endemic

Lesion

Present True positive False positive

Absent False negative True negative

Testing Lesions for Diagnostic Power

0

1

2

3

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Cribra

orbitalia

Porotic

hyperostosis

Humeral

cribra

Femoral cribra Spinal

porosity

Periostitis

Od

ds

Rati

o

False negatives False positives Diagnostic Odds Ratio

Diagnostic Outcome Algorithm

• False negatives = 30%

• False positives = 3%

OROR OR +

Diagnostic Outcome Algorithm

Using only the individuals who died of malaria/anemia:

• False negatives = 15%

• False positives = 3%

Implications

• Malarial lesions: cribra orbitalia, humeral cribra,

femoral cribra, spinal porosity, and periostitis

• Possible etiological factors:

1. Severe malarial anemia

2. Imbalance in bone remodeling

3. General inflammation

Limitations

• Greater range of health problems likely affected

the Ugandan sample

• Malaria tends to co-infect with other diseases,

including dysentery and tuberculosis

• Need to test findings with more clinical samples

Acknowledgements

• Arkansas Graduate Fellowship in Anthropology,

Department of Anthropology, University of Arkansas

• Anatomy Department, Makerere University, Kampala

• Ginesse Listi and Nicole Klein, FACES Lab, LSU

Photo: National Library of Medicine