All posts by Michelle Ziegler

Pregnancy, ‘coffin birth’, and the Black Death

by Michelle Ziegler

The Genoese have always been central in the legend of the start of the Black Death, by their own claim, linking a siege of the Genoese at Kaffa to the spread of the epidemic in the Mediterranean. Last month the first confirmed plague graves in the region of Genoa were reported by Cesana, Benedictow, and Bianucci in the cemetery of the ospitali (hospital) of San Nicolo. The hospital of San Nicolo was located at a node along the route connecting the hilly backcountry of Genoa to the main travel routes of medieval Italy.

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Fetus skeleton. Only fragments were found of the skulls and pelvises for all four individuals. (Cesana, Benedictow, & Bianucci, 2017)

The quadruple grave consisted of a woman in her 30s with full-term fetus in the birth canal (a ‘coffin birth’), and two children aged approximately 3 and 12 years, based on their growth and tooth eruption. Dated stratigraphically to the second half of the 14th century, they are a very rare multiple grave for Northern Italy. No plague pits have been discovered in this region.

They were screened for plague with the RDT dipstick (here and here) that detects the F1 antigen of Yersinia pestis (see also Bianucci et al, 2008 and Pusch et al, 2004). This test has proven quite reliable for archaeological material and is a useful tool for modern diagnosis in resource-poor areas. The RDT dipstick is a more sensitive test than aDNA so we should not expect every positive skeleton by the RDT to produce aDNA but it is a good screening tool prior to aDNA surveys and useful for epidemiological purposes. The adult female, the fetus and the oldest child all gave positive results by the RDT dipstick. I would consider these to be positive plague cases with or without aDNA confirmation. Now I do have one caveat at this point, I’m not ready to assume that the fetus is a true positive, although it is certainly possible. Since it was present in a decaying maternal body with lots of F1 antigen around, the protein could have been absorbed into the fetal bones during the decomposition process. If there is enough aDNA to be detected and readable in the fetal bones, then I would consider it a stronger case.  Regardless, the plague was at least the secondary cause of death for the fetus since it claimed the life of its mother.   Without more genetic testing, we will not know the relationship between the two older children and the woman. They could be one family, although at a hospital they could be of no relation to each other.

Without a more precise date or ancient DNA, we can not predict which plague epidemic produced this grave. Raffaella Bianucci has informed me that these graves will be part of a large aDNA project currently underway, so more information will be available eventually. Then the historical analysis of Ole Benedictow in this article will be very helpful in placing them in a more precise context.

My main interest lies with the pregnant plague victim and her fetus. A coffin birth is caused by the build up of gasses in the corpse that pushes the fetus out of the birth canal. Given that plague victims die of septicemia, possibly infecting the placenta, it’s not all that surprising (at least to me).

Given a high medieval birth rate, I am surprised that more pregnant women have not been found in plague graves. Stephen Ell (1989)  found that 8.5% of all women between ages 15 and 50 were reported as pregnant in the death records he analyzed for three days in an October 1630 epidemic in Venice.    So why haven’t fetuses or newborns been found in more plague graves?

There are a few possible reasons fewer fetuses than expected: early pregnancies are unlikely to leave fetal bones, and in a stacked mass grave, tiny fetal bones would easily get jumbled with all the other bone bits. When fetal bones are found in these mass burials it may be difficult to determine how many fetuses they represent.  Reports from the third pandemic and later may provide a few clues.

So let’s look at a parallel late-term pregnancy infection from 1975 (Welty et al, 1985, 641-2): a 31-year-old Navajo Arizona woman in her 9th month of pregnancy presented at a clinic with a high fever, headache and a tender right axillary node whose aspirate produced the bipolar safety pin looking bacillus suggestive of Yersinia pestis. This was later confirmed by culture and she was started on Streptomycin. On the first day of admission, the baby’s heart rate was already at 200 beats per minute suggesting fetal distress so she was induced, and she delivered a healthy baby boy.  His cord blood was negative for plague and he never developed a plague antibody titer. Two days later the mother’s two and a half-year-old child was admitted with a fever (104 F), cough, headache, and vomiting. Her axial lymph nodes were also positive for Yersinia pestis and she was started on antibiotics as well. All three were recovering well when released from the hospital nine days after the mother’s original admission.

Clearly, antibiotics and the ability to induce the birth made all the difference in this case. The placental blood barrier seems to have held just long enough for a healthy delivery. In the few other cases in the literature, antibiotic treatment appears to rescue the pregnancy, although induction of delivery is recommended if there are signs of fetal distress at 36 weeks of gestation or later. The pre-antibiotic scenario is much grimmer:

“In the preantimicrobial era, plague reguarly resulted in abortion, and the aborted tissues were occasionally infected with plague bacillus. In 1903 Jennings reported 10,000 cases of plague, 14 of which occurred during pregnancy. Four of the mothers survived, but spontaneous abortions or still births occurred in 13 of the patients, including the four survivors. One of the 14 patients was near her expected date of delivery. The child was born apparently well, but the mother died of postpartum hemorrhage. Ten hours after birth, lymphadenopathy was noted in the infant’s groins and axillae and it died one day later.” (Welty et al, 1985, 645)

In another case report from 1975, Mann and Maskowitz (1977) opined that “fetal wastage resulting from a maternal infection with plague probably results from the systemic effects of illness rather than direct placental or fetal infection, although true intrauterine infection with plague as been described.”  Fetal distress detected in the case described above and in the other case reported by Mann and Moskowitz both support a risk to the pregnancy prior to fetal infection. Infection of the fetus and/or placenta would have been a very grave development without access to antibiotics. I can not imagine how a maternal immune system could clear such an infection. At any rate, it seems likely that most infected pregnant women lost their fetus to miscarriage or stillbirth prior to their own death. This would account for a lower than expected number of pregnant women found in plague burials. Given that fetuses and infants are underrepresented in normal cemeteries, it is possible that many of these unbaptized infants in plague times were not buried with the rest of the community.

All of the modern cases would have been managed slightly differently today. The Navaho woman’s entire family would have been examined and given antibiotics immediately. It is hard to believe today they waited until the two-year-old had a 104-degree fever before being examined. Modern plague management guidelines have detailed instructions for treating pregnant women for bubonic and pneumonic plague to maximize safety and limit side effects of the drugs on the fetus (Inglesby et al, 2000). However, saving the mother’s life trumps all considerations if ideal antibiotics are not available or working sufficiently. Prior to 36 weeks of gestation when it can be induced, this is also the best chance the fetus has for survival.


References

Bianucci, R., Rahalison, L., Massa, E. R., Peluso, A., Ferroglio, E., & Signoli, M. (2008). Technical note: a rapid diagnostic test detects plague in ancient human remains: an example of the interaction between archeological and biological approaches (southeastern France, 16th-18th centuries). American Journal of Physical Anthropology, 136(3), 361–367. http://doi.org/10.1002/ajpa.20818

CESANA, D., BENEDICTOW, O. J., & Bianucci, R. (2017). The origin and early spread of the Black Death in Italy: first evidence of plague victims from 14th-century Liguria (northern Italy). Anthropological Science, 1–10. http://doi.org/10.1537/ase.161011

Ell, S. R. (1989). Three days in October of 1630: detailed examination of mortality during an early modern plague epidemic in Venice. Reviews of Infectious Diseases, 11(1), 128–141.

Inglesby, T. V., Dennis, D. T., Henderson, D. A., Bartlett, J. G., Ascher, M. S., Eitzen, E., et al. (2000). Plague as a biological weapon: medical and public health management. Working Group on Civilian Biodefense (Vol. 283, pp. 2281–2290). Presented at the JAMA : the journal of the American Medical Association.

Mann, J. M., & Moskowitz, R. (1977). Plague and pregnancy. A case report. Jama, 237(17), 1854–1855.

Pusch, C. M., Rahalison, L., Blin, N., Nicholson, G. J., & Czarnetzki, A. (2004). Yersinial F1 antigen and the cause of Black Death. The Lancet Infectious Diseases, 4(8), 484–485. http://doi.org/10.1016/S1473-3099(04)01099-0

Welty, T. K., Grabman, J., Kompare, E., Wood, G., Welty, E., Van Duzen, J., et al. (1985). Nineteen cases of plague in Arizona. A spectrum including ecthyma gangrenosum due to plague and plague in pregnancy. The Western Journal of Medicine, 142(5), 641–646.

Presentations on the Plague from the European Association of Archaeologists, Vilnius, Lithuania, 2016

I just discovered that most of the presentations from the “Plague in Diachronic and Interdisciplinary Perspective” session of the Europan Association of Archaeologists meeting in Vilnius, Lithuania on 2 September 2016 are now on YouTube.  I think I have collected them all here. Enjoy 3 hours of plague talks!

Introduction-Plague in diachronic and Interdisciplinary perspective by Marcel Keller


From Mild to Murderous: How Yersinia pestis Evolved to Cause Pneumonic Plague by Wyndham Lathem (30 min)


Reconstructing ancient pathogens – discovery of Yersinia pestis in Eurasia 5,000 Years Ago by Simon Rasmussen (15 min)


Plague in the eastern Mediterranean region 1200-1000 BC? by Lars Walloe (15 min)


Placing the Plague of Justinian in the Yersinia pestis phylogenetic context by Jennifer Klunk (15 min)


A demographic history of the plague bacillus revealed through ancient Yersinia pestis genomes by Maria Spyrou (15 min)


Analysis of a High-coverage Yersinia pestis Genome from a 6th Century Justinianic Plague Victim by Michal Feldman (15 min)


Early medieval burials of plague victims: examples from Aschheim and Altenerding (Bavaria, Germany) by Doris Gutsmiedl-Schumann (15 min)


Fleas, rats and other stories – The palaeoecology of the Black Death by Eva Panagiotakopulu (15 min)


Plague in Valencia, 546: A Case Study of the Integration of Texts and Archaeology by Henry Gruber (15 min)


Germany and the Black Death: a zooarchaeological approach by M.A. Paxinos


Reservoirs of Salt Adapted Yersinia pestis

The Arab Maghreb is one of the most arid environments to host plague reservoirs. The most recent study on the area highlights the proximity of plague foci to salt water, either the Mediterranean Sea, Atlantic Ocean or importantly inland salt lakes (Malek et al, 2016). These inland salt springs, called chotts, are saltier than the ocean. They were specifically able to cultivate Y. pestis from high salt soil and isolate a high salt tolerant strain of Yersinia pestis from Algeria. Plague foci across North Africa were found at an average of 0.89 km from salt water, while the average distance from fresh water is 4.6 km.

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Plague sites 1940-2015. Red = plague sites, Blue = salt water lakes, Yellow = fresh water. Cropped from Malek et al, 2016.

They also note the importance of L-form Yersinia pestis in their environmental samples. L-form bacteria are an understudied cell wall deficient state that quite a few bacteria, including Yersinia pestis, use for long term survival. The L-form of Y. pestis may be important in environmental persistence. Because they are believed to have a slower reproduction rate,  the L-form may also play a role in altering the molecular clock of some strains. To date,  publications that focus on L-form Y. pestis have been in either Russian or Chinese. It seems clear that the L-form is found in some instances in Asia as well. Importantly, some L-form bacteria can regain their cell wall and return to active ‘normal’ growth.

Soil osmolarity is the key feature that allows (or requires) the L-form to persist. Withstanding osmotic tensions is the primary role of the cell wall. Without the cell wall, the cell loses its ‘normal’ shape, taking on a spherical shape determined by hydrophobic-hydrophilic interactions (like oil and water). As the cell membrane is primarily made of phospholipid, its the L-form shape resembles a sturdy oil globule or a liposome (B below). This was apparent by gram stain when the normal individual short rod-shaped (coccobacilli) cells transformed into clusters of completely round (cocci) cells. This was confirmed under the electron microscope where the change is very apparent.

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They also isolated a strain, Algeria3, a descendant of the third pandemic, from soil containing 4% salt, that can grow in a 15% salt broth. Other Algerian isolates that were not found in high salt soils experimentally survived as well in high salt media if the salt content was ramped up in a step-wise fashion. Growth in high salt conditions altered their protein production to increase those related to osmoregulation, metabolism, outer membrane proteins and others of unknown function.  Osmoregulation genes changes are a direct response to the higher salt concentration. The L-form cells are clearly still metabolically active.

Taken together these protein profiles suggest that it has adapted to survive in the salty soil with the ability to adjust its structure and function as necessary to persist.  They note that other plague reservoirs are in regions of the world with salt lakes or other salty sources, but more environmental sampling will be necessary to determine if this is a universal Y. pestis capability. This all has obviously important implications for plague ecology.


Reference

Malek, M. A., Bitam, I., Levasseur, A., Terras, J., Gaudart, J., Azza, S., et al. (2016). Yersinia pestis halotolerance illuminates plague reservoirs. Scientific Reports, 7, 1–10.