The Paleomicrobiology of Malaria Detection

Malaria is arguably one of the most influential infectious diseases in human history. Its been with us as long as we have been human, but as Teddi Setzer shows us in her recent review of detection methods, our abilities to find it in the past leaves a lot to be desired.

The standard method of looking for malaria involves searching for signs of anemia on the skeleton on the hypothesis that the anemia caused by malaria leaves these marks. This is not as clear as it might seem. There have been very few skeletal studies of modern people who have been diagnosed with malaria. There is no medical need; there are much more reliable methods of diagnosing malaria in a living person (or recent cadaver). So, it is unclear how often these lesions form in malaria patients. Other causes of anemia and even scurvy can cause the same or very similar lesions as well.  The number of malarial infections and/or relapses also effect bone changes. Plasmodium falciparium produces a short, virulent disease that may kill before bone changes develop. On the other extreme, a single P. malariae infection can relapse for life, although the anemia is not as severe.  Osteology must be correlated with other information to support the diagnosis. 

Cribra Orbitalia from Jess Beck’s blog Bone Broke

Cribra orbitalia and porotic hyperostosis are the two main indicators sought. Both are caused by bone marrow expansion in an attempt to compensate for the loss of red blood cells. Cribra orbitalia is pitting and extra bone growth in the orbits of the eyes, as seen in the photo.  Porotic hyperostosis causes pitting and thinning of the compact bone ‘shell’ that covers the cranial bones. A  correlation of nutritionally informed osteology with later epidemiology and mosquito incidence in England reviewed in a previous post shows that a convincing case can be made for malaria in ancient remains.

Detection of human genetic traits selected for by malaria such as the Duffy blood group, sickle cell trait, thalassemias, and glucose-6-phosphatase deficiency (G6PD) can with supporting information suggests that the population was once under selection by malaria. Balanced polymorphisms like sickle cell trait can remain in a population for centuries after the selection is gone (by either ecological change or by migration away from the malarious region). While there are some skeletal indicators of some hemoglobinopathies, human ancient DNA analysis would be a more secure method of diagnosis. Care has to be taken to distinguish skeletal changes made by malaria’s hemolytic anemia and the hemoglobinopathy anemias.

Ancient DNA detection of the malaria Plasmodium parasite has been disappointing. To date, only the tropical Plasmodium falciparium, that causes the most severe disease, has been detected by PCR. It is believed that attempts of detect the historically more common Plasmodium vivax have been stymied by the low parasite load in the blood.  The difficulty in finding vivax aDNA is a reminder that pathogens really do need to be in high concentrations within the sample to overcome degradation and be detected by PCR or sequencing technology. As far as I know, there have not been attempts to detect the other three human malarial parasites– Plasmodium ovale, Plasmodium malariae and Plasmodium knowlesi — by aDNA analysis.

Hemozoin crystals in the liver (Source: KMU Pathology Lab)

Modern medicine is devising an ever expanding array of tests for malaria diagnostics and prognostics. However, most of these tests all require fresh (soft) tissue or blood. Immunological methods have not been applied to malaria in archaeological material yet. The most promising detection method for malaria among the newer diagnostics is the detection of the iron containing waste product of the Plasmodium parasite hemozoin. When the parasite feeds on hemoglobin in the red blood cell, toxic iron waste products are processed into the biocrystal hemozoin and excreted into the tissues. In patients with reoccurring or multiple malaria infections, hemozoin will stain their bone marrow black and can be found in liver, spleen, brain and lungs. It can be detected microscopically (as seen above) or by mass spectrometer. Although some other blood parasites also excrete hemozoin, they can be distinguished from the malarial product. 

Despite the advances in diagnosis for existing malaria patients taking advantage of new methods and technologies, archaeological detection has not enjoyed the same success. Building a case for malaria in the past, must rely on an array of data with knowledge of ecology, vectors, and nutritional status of the population in addition to osteological markers of anemia. Hopefully, the detection of hemozoin will eventually be the key to opening up biological studies of malaria in the past. If hemozoin can identify malaria victims, then perhaps focusing the ancient DNA work on hemozoin positive remains will be more successful breaking through the firewall to malaria’s evolution and historical epidemiology. 

 Source:

Setzer, T. J. (2014). Malaria detection in the field of paleopathology: A meta-analysis of the state of the art. Acta Tropica, 140, 97–104. doi:10.1016/j.actatropica.2014.08.010 (open access early editionfinal edition)

See also Jess Brek “Porotic Hyperostosis and Cribra OrbitaliaBone Broke, March 2014. 

Illustrations of the 1896-1897 Influenza Epidemic in Paris

1890 Influenza cartoon (Source: National Library of Medicine)
1897 Influenza cartoon (Source: National Library of Medicine)

This image has been used here at Contagions in various cropped versions as the header and avatar for several years now. I found a couple more related illustrations that are worth sharing and put the illustration in better context. This is an emergency tent hospital erected to handle the epidemic of 1897.  It certainly looks different from the outside as you can see below.

outside
Source: National Library of Medicine
c05532
Source: National Library of Medicine

Based on the date of this newspaper header (12 Jan 1897), this must be illustrations of a lesser known epidemic in 1896-1897 that occurred between the pandemic of 1890 (Russian flu) and that of 1900.

Another view of the scene in the usual header here.

C05532 crop

Reading in August

august

Just a little update on my reading in August. I’ve been jumping around a bit reading on the history of malaria and wetlands.  Lots of interesting bits and pieces!

Books

  • John Aberth. An Environmental History of the Middle Ages: The Crucible of Nature, 2013.
  • Gregory of Tours (d. 594): Glory of the Confessors 
  • Gregory of Tours (d. 594): The Life of the Fathers
    • Looking at what diseases people are seeking cures for primarily at the shrines of the saints.
  • William McNeill, Plagues and Peoples. 1976.
    • I reread this book about every ten years, so I’m working my way through it over lunch at work at the present. Odd to reread a book I first read in the late 1980s as a student.  Its surprising how well it holds up, but it is now out of date in biology, history and anthropology. It really can’t be used to represent modern views on either infectious disease biology or history. We really need a new, updated edition!  Just to give a few examples, HIV hadn’t even been identified in 1976 (as McNeill mentions in the preface of the 1998 edition) and antibiotic resistance and ‘(re)emerging infectious diseases’ were not considered critical problems (although both had begun to appear).
  • Robert Sallares, Malaria and Rome: A History of Malaria in Ancient Italy. 2002 (in progress)
 Standout Papers – (more or less in order they were read)
  • Couser, J. (2010). The Changing Fortunes of Early Medieval Bavaria to 907 ad. History Compass, 8(4), 330–344. doi:10.1111/j.1478-0542.2009.00671.x
  • King, G., & Henderson, C. (2013). Living cheek by jowl: The pathoecology of medieval York. Quaternary International, xxx, 1–12. doi:10.1016/j.quaint.2013.07.032
  • Förster, F., Großmann, R., Hinz, M., Iwe, K., Kinkel, H., Larsen, A., et al. (2013). Towards mutual understanding within interdisciplinary palaeoenvironmental research: An exemplary analysis of the term landscape. Quaternary International, 312(C), 4–11. doi:10.1016/j.quaint.2013.07.045
  • Rippon, S. (2009). ‘Uncommonly rich and fertile’ or “not very salubrious?” The Perception and Value of Wetland Landscapes. Landscapes, 10(1), 39–60.
  • Bankoff, G. (2013). The“English Lowlands” and the North Sea Basin System: A History of Shared Risk. Environment and History, 19(1), 3–37.
  • Justin T. Noetzel. Monster, Demon, Warrior: St Guthlac and the Cultural Landscape of the Anglo-Saxon Fens. Comitatus: A Journal of Medieval and Renaissance Studies, Volume 45, 2014, pp. 105-131.
  • O’Sullivan, L., Jardine, A., Cook, A., & Weinstein, P. (2008). Deforestation, mosquitoes, and ancient Rome: Lessons for today. BioScience, 58(8), 756–760.