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Infectious Disease Part 2: Malaria and Associated Anaemic Conditions

5 Oct

This second post, and the first part, deal with biomolecular approaches and research studies in detecting  the presence of infectious diseases in human bone from archaeological material.  The recent coming of age of biomolecular techniques, as applied to archaeological material, has provided a rich and complex source of information in helping to uncover how infectious diseases spread in the historic and prehistoric past.  The second post, here, describes recent research focused on Malaria and associated anaemic conditions, including Sickle Cell Anaemia and Thalassaemia.  The first post can be found here.

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It has long been realised that malaria can only be recognised in skeletal remains via indirect evidence of presentation of the following pathological lesions- porotic hyperostosis, cribra orbitalia and marrow hypertrophy- which are taken as evidence of the presence of anaemia, the main contributor of mortality in malarial victims (Roberts & Manchester 2010).  However there is no pathognomonic bone lesion for either Plasmodium vivax or P. falciparum, the main human species of malaria causing Plasmodium genus  (Gowland & Western 2012: 303, Roberts & Manchester 2010: 233), and the above skeletal lesions have varying aetiologies including anaemia, osteitis, parasitic infection, and other interrelated deficiency diseases which are still not clearly understood (Gowland & Western 2012: 302).  To securely diagnose malaria in skeletal material, DNA identification of the Plasmodium genus must take place, and even then current Polymerase Chain Reaction (PRC) tests ‘do not appear to be able to amplify routinely the DNA of malaria pathogens from ancient bones’ (Gowland & Western 2012: 302).

Recent immunological techniques to identify antigens have also been used to isolate and identify P. falciparum, although false positives can occur as a result of contamination or diagenetic factors(Gowland & Western 2012: 302).  Gowland & Western (2012) have recently proposed a spatial epidemiological model for malarial spread in Anglo-Saxon England, which highlights the re-surging interest in malaria in the modern context as well as one affecting a past population.  This holistic approach used GIS data with diagnosed porotic hyperostosis in skeletal remains, mosquito (Anopheles atroparvus) habitat information and historical data in presenting a locality data set for malaria infected individuals (Gowland & Western 2010: 304-305).  The modelling of palaeopathological, climatic, and historical data, provides new information on disease range, mechanism of transmission, and infection localities.  However, there are also complicating factors in assessing and diagnosing malaria from other diseases, as noted below (Roberts & Manchester 2010: 234).

Particularly important are two inherited haemolytic anaemia’s, thalassaemia and sickle-cell anaemia, who are characterised by abnormal haemoglobin and increased destruction of red blood cells (Jurmain et al. 2011: 312, Roberts & Manchester 2010: 232).  Thalassaemia is a genetically determined disorder which is caused by a ‘problem of haemoglobin synthesis’ (Roberts & Manchester 2010: 233).  This results in failure or depression of synthesis of the chain, this leads to pale cells with low hemoglobin content which are then rapidly destroyed once formed.  There are three grades of the disease, minor, intermediate and major, the last of which includes severe anemia and possible bone changes; the range of the disease is typically centered in the Mediterranean, Middle East and Far East (Roberts & Manchester 2010: 233).  The importance is that it is seen as an adaptive response to malaria infection through the development of this heritable disease; that the high red blood cell turnover stalls and negates any effect of malarial infection.  Archaeological evidences comes from Greek, Turkish and Cypriot populations deriving from marshy contexts, which are ideal breeding grounds for mosquitoes, the prime vector for malaria (Roberts & Manchester 2010: 233).

Sickle-cell anaemia occurs as a result of the deformation and destruction of red blood cells which leads to over enlargement of bony centres (centered on the skull, pelvis, vertebrae) and over-activity of marrow production as the body produces more red blood cells (Waldron 2009).  This inheritable disease range is mainly located in Central and Eastern African populations who have high rates of the disease, but also affects Indian, Middle Eastern, and Southern European populations (Roberts & Manchester 2010: 234).  Jurmain et al. (2011: 312) remark that the sickle-cell allele hasn’t always been effective in malarial negation in human populations, and primarily came to prominence during the advent of agriculture, and in particular during the last 2000 years in Africa.  The origin of the mutation of the allele responsible, HB5 in haemoglobin, has been dated to 2100 to 1250 years ago in African populations (Jurmain et al. 2011: 312).  Although malaria infection has only relatively recently affected human populations, it has become a powerful selective force that still affects large portions of the world’s population today.

In conclusion, biomolecular approaches to archaeological and osteological remains are vital in unraveling past populations and the natural world (Jurmain et al. 2011).  The interactions between wild and domesticated animals, humans, insects and the environment are a prerequisite for understanding the mode of transmission and virulence of infectious diseases (Barnes et al. 2011, Gowland & Western 2012, Jurmain et. al 2011).  Yet, we must take into consideration the difficulties in understanding infectious disease; examples of the osteological paradox are ever present, understanding the aetiology of bone changes, and the context of genetic differences between populations must be noted whilst PCR amplification, aDNA detection and genome explorations methods must be continually improved for clearer results (Li et al. 2011, Schurch et al. 2011, Spigelman et al. 2012, Tran et al. 2011); this approach must be multidisciplinary in understanding past and present populations (Jurmain et al. 2011, Roberts & Manchester 2010, Waldron 2009).

The modern world has changed, and the boundaries that once protected various human populations has changed dramatically with cheap air travel and vast population movement; this is unprecedented in both history and prehistory, and in population density and scale, but also at the genetic level in human genetic variation (Hawks et al. 2007, Jurmain et al. 2011: 311).  The eradication of smallpox, the Bill and Melinda Gates foundation in fighting malaria, and the ongoing WHO (World Health Organisation) case against polio (Branswell 2012: 50) are strong examples of what can be achieved worldwide.  By building a past population profile of the effects of infectious disease, we are better prepared for the fight tomorrow.

Bibliography:

Barnes, I., Duda, A., Pybus, O. G. & Thomas, M. G. 2011. Ancient Urbanization Predicts Genetic Resistance to Tuberculosis. Evolution. 65 (3): 842-848.

Branswell, H. 2012. Polio’s Last Act. Scientific American. 306 (4): 50-55.

Gowland, R. L., & Western, A. G. 2012. Morbidity in the Marshes: Using Spatial Epidemiology to Investigate Skeletal Evidence for Malaria in Anglo-Saxon England (AD 410- 1050). American Journal of Physical Anthropology. 147: 301-311.

Hawks, J., Wang, E. T., Cochran, G. M., Harpending, H. C. & Moyzis, R. K. 2007. Recent Acceleration of Human Adaptive Evolution. Proceedings of the National Academy of Sciences. 104 (52): 20753-20758.

Jurmain, R., Kilgore, L. & Trevathan, W. 2011. The Essentials of Physical Anthropology, International Edition. Belmont: Wadsworth.

Li, Y., Carroll, D. S., Gardner, S. N., Walsh, M. C., Vitalis, E. A. & Damon, I. K. 2007. On the Origin of Smallpox: Correlating Variola Phylogenics with Historical Smallpox Record. Proceedings of the National Academy of Science. 104 (40): 15787-15792.

Roberts, C. & Manchester, K. 2010. The Archaeology of Disease. Stroud: The History Press.

Schurch, A. C., Kremer, K., Kiers, A., Daviena, O., Boeree, M. J., Siezen, R. J., Smith, N. H., & Soolingen, D. V. 2010. The Tempo and Mode of Molecular Evolution of Mycobacterium Tuberculosis at Patient-to-Patient Scale. Infection, Genetics and Evolution. 10 (1): 108-114.

Spigelman, M., Shin, D. H., & Gal, G. K. B. 2012. The Promise, the Problems and the Future of DNA Analysis in Palaeopathology Studies. In Grauer, A. L. (ed). A Companion to Palaeopathology. Chichester: Blackwell Publishing Ltd.  pp.133-151.

Tran, T., Aboudharam, G., Raoult, D., & Drancourt, M. 2011. Beyond Ancient Microbial DNA: Nonnucleotidic Biomolecules for Palaeomicrobiology. BioTechniques. 50: 370-380.

Waldron, T. 2009. Palaeopathology. Cambridge: Cambridge University Press.