Category Archives: microbiology

Multi-strain Plague Blooms Over Landscapes

Two articles have come to my attention over the couple months that argue strongly for an environmental role in plague epidemics/epizootics over clonal expansion. Taken together these studies suggest that multiple strains of Yersinia pestis percolate out of multiple reservoirs at the same time.

Sites of Madagascar cases, 2007 (Riehm et al, 2015)
Sites of Madagascar cases, 2007 (Riehm et al, 2015)
Strains isolated in Madagascar, 2007 (Riehm et al, 2015)
Strains isolated in Madagascar, 2007 (Riehm et al, 2015)

The strongest support comes from Madagascar where ten MLVA defined strains from 93 human clinical specimens representing the two major groups of Yersinia pestis (based on, if I recall correctly, their introduction source) all emerged within one single year, 2007, scattered over a large range of the central island. These ten strains represent eight previously known strains and two discovered in this investigation. As the map shows, several locations had cases from more than one lineage.  This pattern does not suggest to me that one strain was more successful than another; there is no new mutation that allowed one strain to erupt on the scene or transmission advantage caused by chance or mutation. (Yes, chance does play a role sometimes.) That one strain is more widespread than another probably represents years of enzootic spread and so multiple emergences of a more common strain. With multiple strains emerging at the same time, there is relatively little clonal or territorial expansion, and no reason to expect a major selective advantage by any particular strain. They are emerging where ever the right environmental conditions exist. This study is not directly informative on the underlying epizootic. There may have been even more strain diversity in the epizootic.

There are at least two relevant findings for future surveillance. First, these strains were genotyped directed from DNA in clinical specimens without culturing the specimen. This means that specimens that previously were difficult to culture can still be genotyped and it also should be safer for lab staff to handle. It suggests again that they need a new case classification system since only culturable isolates are considered confirmed. As encouraging as this is, the bad news for reservoir surveillance is that they will have to monitor very large zones based on climate and other environmental factors instead of just trying to project the direction of an ongoing outbreak.

This is supported by another study published in May by Jennifer Lowell’s team on plague in the western US. They analyzed 34 isolates of Yersinia pestis collected from fleas, humans, cats, and a variety of other animals between 1980 and 2006 primarily in Colorado (21) and some scattered sites across the southwest. In Colorado isolates geographically close but temporally spaced showed an evolutionary relationship demonstrating that they had evolved in place over seven years. Mountain isolates were also distinctive between valleys and on the plains suggesting that they evolved in isolation.

During the initial introduction of Yersinia pestis to a region, there is a rapid spread of a single clone but following this, there the creation of local reservoirs with evolution occurring in place. Subsequent epizootics emerge from these new reservoirs and remain small. It follows that large epizootics are usually the emergence of several reservoirs stimulated by the right environmental conditions.

What I take from this is the idea that large scale spread of epizootics or epidemics over different ecological regions require human assistance. There is a anthropogenic factor to the largest epizootics/epidemics. Left to their own means, epizootics remain local spreading only as far as the contiguous environment allows. Some agent, usually humans, must carry them between permissive environments. It is possible that the permissive environment will be urban as it was in Madagascar in the 1990s (Vogler et al, 2013).

Now thinking historically, what we need is serial aDNA results from the same city over many centuries. London and Marseille would be good options, so would Constantinople and Alexandria. With enough aDNA samples it should be possible to estimate how many introductions of Yersinia pestis from the Asia occurred for each pandemic and to discern a role for European or Mediterranean local reservoirs. These modern studies are absolutely necessary to make sense out of the patterns that will eventually emerge when we have enough aDNA specimens.

References:

Riehm, J. M., Projahn, M., Vogler, A. J., Rajerison, M., Andersen, G., Hall, C. M., et al. (2015). Diverse Genotypes of Yersinia pestis Caused Plague in Madagascar in 2007. PLoS Neglected Tropical Diseases, 9(6), e0003844. doi:10.1371/journal.pntd.0003844.s002 (h/t to Matt Wilson for this one!)

Lowell, J. L., Antolin, M. F., Andersen, G. L., Hu, P., Stokowski, R. P., & Gage, K. L. (2015). Single-Nucleotide Polymorphisms Reveal Spatial Diversity Among Clones of Yersinia pestis During Plague Outbreaks in Colorado and the Western United States. Vector Borne and Zoonotic Diseases (Larchmont, N.Y.), 15(5), 291–302. doi:10.1089/vbz.2014.1714

Vogler, A., Chan, F., Nottingham, R., Andersen, G., Drees, K., Beckstrom-Sternberg, S., Wagner, D., Chanteau, S., & Keim, P. (2013). A Decade of Plague in Mahajanga, Madagascar: Insights into the Global Maritime Spread of Pandemic Plague mBio, 4 (1) DOI: 10.1128/mBio.00623-12

Spring Reading

spring1
It has been a busy spring. I haven’t had a chance to blog as much as I would have liked to, but I have done quite a bit of reading. Some of my reading has been on the complex world of the first plague pandemic. To say that it was transformative would be an understatement.  One of the social questions for the first plague pandemic is how does plague and other natural disasters effect a population that is the midst of conversion?  When the Black Death came it encountered a fully Christian and Muslim world, but not so during the first pandemic. Most of Europe was not yet Christian in 541. There were some Jews, Christians of several varieties, Roman pagans, Germanic pagans, Celtic pagans, Zoroastrians, North African and Middle Eastern pagans, etc. Yet at the end of the pandemic period, Islam is born (and fast growing) and Christianity is dominant in Europe (and united by Rome). The plague began in a polytheistic world and ended in a monotheistic one. What role did the plague play, if any? Yet to be determined. This really isn’t a peripheral issue. Every writer of the first pandemic was involved in this transformation (winners and losers) in some way and it effected how they wrote about the plague and other calamities. So I have a lot of reading to do; below is a start and a few other things that caught my attention.

Books:

Marilyn Dunn. (2010) The Christianization of the Anglo-Saxons, c. 497- c.700: Discourses of Life, Death and Afterlife.

Marilyn Dunn (2013) Belief and Religion in Barbarian Europe, c. 350-700. Bloomsbury.

Peter Brown (2015) The Ransom of the Soul: Afterlife and Wealth in Early Christianity. Harvard University Press.

Peter Heather (2013) The Restoration of Rome: Barbarian Popes and Imperial Pretenders. Oxford University Press.

Articles:

Balbir Singh and Cyrus Saneshvar (2013) Human Infections and Detection of Plasmodium knowlesi. Clinical Microbiology Reviews. 26 (2): 165-184.

Runfola, J. K., House, J., Miller, L., Coltron, L., Hite, D., Hawley, A., et al. (2015). Outbreak of Human Pneumonic Plague with Dog-to-Human and Possible Human-to-Human Transmission — Colorado, June–July 2014. MMWR. Morbidity and Mortality Weekly Report, 64(16), 429–434.

Smith-Guzmán, N. E. (2015). Cribra orbitalia in the ancient Nile Valley and its connection to malaria. International Journal of Paleopathology, 10, 1–12. doi:10.1016/j.ijpp.2015.03.001

Benovitz, N. (2014). The Justinianic plague: evidence from the dated Greek epitaphs of Byzantine Palestine and Arabia. Journal of Roman Archaeology. doi:10.1016/S1473-3099(13)70323-2)

Bernard Bachrach, (2007) Plague, Population, and Economy in Merovingian Gaul. Journal of the Australian Early Medieval Association. 3: 29-57.

Sarris, P. (2002). The Justinianic plague: origins and effects. Continuity and Change, 17(02), 169–182. doi:10.1017/S0268416002004137

Newfield, T. P. (2015). Human–Bovine Plagues in the Early Middle Ages. Journal of Interdisciplinary History, 46(1), 1–38. doi:10.1179/146141010X12640787648612

Inskip, S. A., Taylor, G. M., Zakrzewski, S. R., Mays, S. A., Pike, A. W. G., Llewellyn, G., et al. (2015). Osteological, Biomolecular and Geochemical Examination of an Early Anglo-Saxon Case of Lepromatous Leprosy. PLoS ONE, 10(5), e0124282. doi:10.1371/journal.pone.0124282.s001

Shanks, G. D., & White, N. J. (2013). The activation of vivax malaria hypnozoites by infectious diseases. The Lancet Infectious Diseases, 13(10), 900–906. doi:10.1016/S1473-3099(13)70095-1

Dick, H. C., Pringle, J. K., Sloane, B., Carver, J., Haffenden, A., Stephen Porter, H. A., et al. (2015). Detection and characterisation of Black Death burials by multi-proxy geophysical methods. Journal of Archaeological Science, 1–50. doi:10.1016/j.jas.2015.04.010

Lowell, J. L., Antolin, M. F., Andersen, G. L., Hu, P., Stokowski, R. P., & Gage, K. L. (2015). Single-Nucleotide Polymorphisms Reveal Spatial Diversity Among Clones of Yersinia pestis During Plague Outbreaks in Colorado and the Western United States. Vector Borne and Zoonotic Diseases (Larchmont, N.Y.), 15(5), 291–302. doi:10.1089/vbz.2014.1714

Neil, B. (2013). The Papacy in the Age of Gregory the Great. A Companion to Gregory the Great, 3–28.

Brogiolo, G. P. (2015). Flooding in Northern Italy during the Early Middle Ages: resilience and adaption. Post-Classical Archaeologies, 5, 47–68.

Kostick, C., & Ludlow, F. (2015). The dating of volcanic events and their impact upon European society, 400-800 CE. Post-Classical Archaeologies.  5, 7–30.

Riehm, J. M., Projahn, M., Vogler, A. J., Rajerison, M., Andersen, G., Hall, C. M., et al. (2015). Diverse Genotypes of Yersinia pestis Caused Plague in Madagascar in 2007. PLoS Neglected Tropical Diseases, 9(6), e0003844. doi:10.1371/journal.pntd.0003844.s002

Makundi, R. H., Massawe, A. W., Borremans, B., Laudisoit, A., & Katakweba, A. (2015). We are connected: flea–host association networks in the plague outbreak focus in the Rift Valley, northern Tanzania. Wildlife Research, 42(2), 196. doi:10.1071/WR14254

A Migration Age Anglo-Saxon Leper

Paleomicrobiology and isotopic analysis has the ability to completely change what we know of past infectious diseases. A study published this month on a fifth century Anglo-Saxon skeleton is one of the most complete I have read.

Lesions on skeletons found at Great Chesterfield in Essex, England, suggested possible leprosy. To confirm this diagnosis, they chose one skeleton that is nearly complete and in good shape for further analysis.

Grave GC86 from Great Chesterford, excavated in a rescue archaeology operation in 1953-4.
Grave GC86 from Great Chesterford, excavated in a rescue archaeology operation in 1953-4. (Inskip et al, 2015)

The skeleton (GC96) shown to the right is of a 25 to 35-year-old male buried in modestly furnished grave in an area of the cemetery with other visibly disabled people. Radiocarbon dating places these remains at AD 415-545, and thus Migration Age for the Anglo-Saxons. The Great Chesterford cemetery is located roughly in an approximate border area between the kingdom of the East Saxons and East Angles at the site of a ford of the River Cam (or Granta) downriver from Cambridge. He was buried with a slender knife secured by a belt with an oval buckle. Over his left shoulder, a spear and a conical ferrule were found.  Lesions consistent with lepromatous leprosy were found on the lower legs with extensive remodeling of the right foot. A bronze shoelace tag found near the right foot suggests the diseased foot covered with a shoe.  Given the lesions found on the foot and lower legs, the ferrule may have capped a walking staff. His facial bones were missing losing a common, distinctive site of leprosy lesions. The disorganized and rough appearance of new bone growth suggest that the lesion was active at the time of death.

Profile of the mycolic acids extracted from the indicated bones.
Profile of the mycolic acids extracted from the indicated bones. (Inskip et al, 2015)

Selections of bone were taken and powdered to extract aDNA and for lipid analysis. Mycobacterium species that cause leprosy and tuberculosis have distinctive lipid profiles that have been successfully extracted and identified by archaeological remains in the past. Their analysis of lipids from the bones confirmed the presence of Mycobacterium leprae and excluded the presence of Mycobacterium tuberculosis.  The aDNA analysis confirmed identified the presence of Mycobacterium leprae strain 3I-1, that has been previously found in later medieval England, Denmark and Sweden. Inskip et al (2015) suggest a possible Scandinavian origin for the strain.  The VNTR analysis used to produce ‘genetic fingerprints’ shows that this strain of M. leprae is unique among other ancient isolates and should be useful in the comparative analysis of other early remains. Other remains in the same cemetery have similar lesions and will be investigated in the future.

Isotopic analysis of his tooth enamel provide an indication of childhood location and adult nutrition. Carbon analysis showed a diet of primarily C3 plants, consistent with southern Britain. Analysis of oxygen and strontium isotopes suggest he did not spend his childhood in the area of Great Chesterford.

The combination of the two isotopes gives his best probable origin to be between north-central France and the north-central Germany, in other words, the region of the Anglo-Saxon homeland. A continental origin coupled with the dating range between 415 and 545 suggests that he was part of the migration of the peoples who later called themselves Anglo-Saxons. He was likely no more Scandinavian than any of the other migration era ‘English’. This is further supported by a relatively high level of leprosy (by osteological analysis) in medieval city of Schleswig, the very area where the Angles are most specifically located. Further analysis of migration era remains should refine the origins of this strain of leprosy and determine its frequency.

Reference:

Inskip, S. A., Taylor, G. M., Zakrzewski, S. R., Mays, S. A., Pike, A. W. G., Llewellyn, G., et al. (2015). Osteological, Biomolecular and Geochemical Examination of an Early Anglo-Saxon Case of Lepromatous Leprosy. PLoS ONE, 10(5), e0124282. doi:10.1371/journal.pone.0124282.s001

Kristina Killgrove, 14 May 2015 “Earliest Case of Leprosy in Britain reveals Scandinavian Origins of the Disease”, Forbes.com

SIMON MAYS, SONIA R. ZAKRZEWSKI, SARAH A. INSKIP, STEPHANIE WRIGHT and JOANNA R. SOFAER. (2015) Anglo-Saxon concepts of dis/ability: placing disease at Great Chesterford in its wider context. Poster at The 84th Annual Meeting of the American Association of Physical Anthropologists.