Siberian Mummy Yields 300-year-old Smallpox DNA

Five mummies in one grave. Benigini et al. NEJM, 2012. DOI: 10.1056/NEJMc1208124

It was the mass grave that got their attention. Four bodies crammed into one casket, with one child outside but with the casket. Multiple graves are not common in Yakutia, Siberia. Examination of the late 17th to early 18th century mummies indicates that burial came quickly after death. The casket contains one adult male over age 30, an adult female, an adult female under age 23,  a male child about 5 years old, and outside the casket a child about 4 years old.

The French and Russian team led by Philippe Biagini undertook pathological and genetic analysis of all five mummies. They were able to confirm that the older woman is the mother of  the young adult woman and the adult male. They took lung and tooth specimens from each mummy at the site (in situ). Finding iron inclusions in the lungs of the young female (mummy 2), suggested to the team that she suffered a pulmonary hemorrhage shortly before death. They don’t say how they jumped from there to screening for smallpox or what other pathogens were considered.  Oddly, they make no mention of any smallpox lesions on the mummy. (Without other bioarchaeological data, is it possible that this team only received the tooth and lung specimens, but not the remainder of the mummy?)

The DNA was divided among three labs. Three short sections of Variola  (smallpox) genome were amplified by at least two labs each. They failed to amplify long stretches of the virus, suggesting that there are no intact virons left in the mummy. Their phylogenetic analysis grouped this virus, PoxSib, with Variola but distinct from both clade 1 and clade 2. They suggest that PoxSib could be an ancestral strain to both clade 1 and clade 2 or a strain that has not been previously sampled. Biagini et al. suggest this virus may have come to Siberia with the Russian conquest in early 18th century, possibly connected with a documented outbreak in 1714. This grave comes from the same culture as previously analyzed graves that isolated the first ancient whooping cough.

Reference:

Biagini, P., Thèves, C., Balaresque, P., Géraut, A., Cannet, C., Keyser, C., Nikolaeva, D., Gérard, P., Duchesne, S., Orlando, L., Willerslev, E., Alekseev, A., de Micco, P., Ludes, B., & Crubézy, E. (2012). Variola Virus in a 300-Year-Old Siberian Mummy New England Journal of Medicine, 367 (21), 2057-2059 DOI: 10.1056/NEJMc1208124 See supplemental appendix for most of the detail.

When Yellow Fever Came to the Americas

“Yellow Jack”, Cornhill Mag., 1892

In the early Americas, nothing scared people more than when Yellow Jack came knocking at the door of their city. Yellow Jack, or as we know it better today Yellow Fever, has rightly been called the plague of the Americas.

It has long been assumed that yellow fever came to the Americas with its vector, Aedes aegypti, in the hold of slave ships. These ships would have been an irresistible feast to the mosquito. Yet, little was known about the origin, locations, and dates of transmission to South America. Juliet Bryant, Edwarld Holmes and Alan Barrett (2007) looked to DNA analysis of yellow fever virus (YFV) strains from 22 countries ( 14 African and 8 South American) to resolve and date the phylogentic tree for YFV. They analyzed 133 isolates from humans and animal hosts collected over a 75 year period.

Bryant, Holmes and Barrett (2007: e75) made four clear observations.

1. The American strains represent a single clade (monophyletic).
2. There are two distinct sub-clades in east and west South America respectively.
3. The South American clade is most similar to the West African isolates.
4. The East African clade is the most distinctive.

These observations support an east or central African origin for the Yellow Fever Virus dominated by enzootic transmission. Its development parallels the transmission of its vector Aedes aegypti.

The split between the east and west African clades has been calculated to an average distance of 723 years (roughly 1284 AD). The West African isolates are the most diverse in Senegal, suggesting this was an early focus for West African YSF. From West Africa Yellow Fever was transmitted to Brazil a calculated average of 470 years ago (roughly 1537 AD). Early Portuguese seamen frequented this part of Africa and Brazil was their largest colony, founded in 1500. This suggests that Yellow Fever was transmitted to Brazil virtually from the beginning of the Portuguese colony. It is possible that Yellow Fever was one of the imported diseases brought by the Portuguese that decimated native Brazilians before large-scale importation of Africa slaves. The South American clade split into eastern and western populations when it was transmitted to Peru a calculated average of 306 years ago (roughly 1700). There is no evidence of transmission back to Africa or other areas where Aedes aegypti have spread in Asia. Byrant, Holmes and Barrett (2007) argue that sylvatic transmission is the primary means of maintaining YSF in South America. They note that there hasn’t been an urban epidemic of YSF in South America since 1928, unlike the annual urban outbreaks in West Africa.

Auguste et al (2010) confirmed the overall structure of the YSF phylogenetic tree in the Americas, including its Brazilian origin in the Americas. Their analysis of strains collected over the last decade also confirm that Brazil is the reservoir and origin for most strains in the Americas today with the Peruvian strains remaining primarily localized in Peru and neighboring Bolivia. The analysis of Auguste et al (2010) also supports enzootic maintenance and local evolution in areas of spread from Brazil such as Trinidad and Columbia.

What I find most surprising about the YSF tree is its relative youth. This all suggests that Yellow Fever originated in the Middle Ages and probably did not circulate outside of local areas of central Africa until the late medieval period. We still have a lot of learn about the landscape epidemiology of yellow fever including possible vertical transmission among mosquitoes and the importance of difference primate species as reservoirs. Although we have had an effective vaccine for decades, yellow fever is still a very clear and present danger in both the Americas and Africa.

References:

J E Bryant, E C Holmes, & A D T Barrett (2007). Out of Africa: A Molecular Perspective on the Introduction of Yellow Fever Virus into the Americas PLOS Pathogens, 3 (5) : doi:10.1371/journal.ppat.0030075

Auguste, A.J., Lemey, P., Pybus, O.G., Suchard, M.A., Salas, R.A., Adesiyun, A.A., Barrett, A.D., Tesh, R.B., Weaver, S.C. & Carrington, C.V.F. (2010). Yellow Fever Virus Maintenance in Trinidad and Its Dispersal throughout the Americas, Journal of Virology, 84 (19) 9977. DOI: 10.1128/JVI.00588-10

Contagions Round-up 24: The Links of Summer

Summer hasn’t been the kindest to the blogosphere (or at least parts of it I cover). It seems unnaturally quiet. Hopefully this means some of the regular bloggers have big projects going on that we will eventually hear about.  Still, covering over a month of posts, there is quite a bit here for your mid-summer reading.

Let’s start out with Bora Zivkovic’s review of the history and future of science blogging from his blog A Blog Around the Clock. Always good to get history from the people who make it!

Vincent Racaniello of The Virology Blog posted on the origins of the fuss over the H5N1 influenza studies from this spring, and a funky new RNA-DNA hybrid virus.

Zoonotica writes about the new fad of fish pedicures and zoonotic diseases. I have to admit that one day I’d like to try this but only if the conditions change. I do wonder if there could be medical uses for these fish (bred specially for medical purposes) doing wound care not unlike the specialty uses that leeches can be put to today.

No Shit! Connor Bamford of Rule of 6ix write about a new method of studying diarrhea in the lab. This post was a follow-up to his twitter journal club article on the microbial biogeography of public toilets.

Captain Skellet of a Schooner of Science writes about the domestication of Aspergillus to make sake.

You might want some sake before reading my post on Japanese use of plague during World War II, here at Contagions. Plague and war go together in strange ways, even the Black Death was reputed to have started (for Europeans) at the siege of Caffa in 1346 discussed in another post this summer.

Michael Walsh of Infection Landscapes continues his series on eukarytoic parasites with liver flukes. From his miniblog Germscape he posted a map of emerging zoonotic diseases 1940-2012 and map of the zoonotic burden on poor livestock farmers.

Mystery Rays from Outer Space also posted a map of emerging zoonoses. Interesting to see clusters in so many ‘first world’ countries: the US, Europe and Japan.

Maryn McKenna of Superbug has been on the trail of the links between drug resistant UTIs and antibiotics in chicken production. This seems to be the opening salvo in a major investigative series, so hang on for a wild ride. Maryn also suggests Zoobiquity as a summer read.

Spirochetes Unwound writes about the difficulty of testing for leptospirosis,  what Borrelia burgdorferi (Lyme disease) needs to escape the tick gut, and the discovery of syphilis aDNA in 16th-17th century infants.

Meanwhile, Tara Smith of Aetiology has been teaching zombie epidemiology while doing some important public outreach, and offers some epidemiology summer reading suggestions.

Turning to history of medicine, Debroah Blum of Elemental, writes about naturally poisoned cattle, the radioactive assassins poison, and the chemistry of chocolate chip cookies.

Marri Lynn of Wonders & Marvels wrote about the mechanical metaphors of 16th century anatomical writing.

Puff the Mutant Dragon is back at his blog writing about how the constant calls for more STEM training doesn’t match job availability, about chemicals in vaccines, and the chemistry of illegal drugs.

What makes a Super-Spreader?

Parameters that should be theoretically equal often aren’t so in the real world. Ideally everyone should have the same potential to transmit an infection during a given outbreak, but it has long been observed that this isn’t true. Super-spreaders play an extraordinary role in driving outbreaks of infectious disease. A super-spreader is a person who transmits an infection to a significantly greater number of other people than the average infected person. The occurrence of a super spreader early in an outbreak can be the difference between a local outbreak that fizzles out and a regional epidemic.

Super-spreaders have been known since infamous Typhoid Mary spread typhoid fever to 51 people over seven years with just an asymptomatic infection [1]. For much of the time since then, they have been treated as oddities, puzzles that could be cracked as if there was necessarily something intrinsically wrong with them. It turns out that its a lot more complicated than personal immunity or genetics. Eventually new models arose like the “20/80″ rule that says that 20% of cases are responsible for 80% of the transmission and formed a core ‘high risk’ group [2,3]. This model works well for some diseases but not all.

For pathogens that do rely on super-spreaders, the majority of cases will not transmit the infection to anyone [3]. This can lead to a sense of false security because it seems poorly communicated. As Galvani and May assert, “heterogeneously infectious emerging disease will be less likely to generate an epidemic, but if sustained, the resulting epidemic is more likely to be explosive”[3].  Super-spreaders tend to beget more super-spreaders, although most of the cases they generate will still not transmit the infection to anyone. For example, a super-spreader begets 30 cases, 3 (10%) of which become new super spreaders.  The rest may transmit to 0-1 people.  Even with super-spreaders it superficially doesn’t look very efficient but it can create an explosive epidemic.

Super-spreading has been documented for HIV, SARS (Sudden Acute Respiratory Syndrome), measles, malaria, smallpox and monkeypox, pneumonic plague, tuberculosis, Staphylococcus aureus, typhoid fever, and a variety bacterial sexually transmitted diseases [1,2,3]. For the sexually transmitted diseases (STDs) we tend to talk more about risk groups than super-spreaders but this still what they are. Case studies are easily found for most of the diseases listed above, including measles super-spreaders who infect known vaccinated children [1].

So what makes a super-spreader? Richard Stein recently summarized what we know so far. Some pathogens have virulence factors that have been associated with super-spreading. I am not aware of many pathogen genes or genotypes associated with super-spreading. So far predominantly extra-pathogen factors have been associated with super-spreading.

Co-infection is turning out to be the most interesting factor in producing super-spreaders. Consider Typhoid Mary, her normal flora may have kept her both asymptomatic and promoted her super-spreader activity. Its been known for some time that co-infection with another sexually transmitted disease increases transmission of HIV. There are less obvious co-infections. It has been shown that a rhinovirus, a common cold virus, infection dramatically increases the airborne spread of Staphylococcus aureus, producing ‘cloud-adults’ or ‘cloud-babies’ [1].

Immunological factors are often suspected in super-spreaders. People with a decreased immunity for any reason may carry a higher pathogen load that can increase environmental pathogen shedding. It has also been suspected that conditions that cause sneezing like seasonal allergies could spread pathogens colonizing the respiratory system[1].

Host behavior is a known factor in some super-spreading events. Transmission of STDs depends on contact rates and so contact frequency and length matters, [1]. People who ignore instructions like wearing a condom or not working in food service can become super-spreaders.  Education aimed at high risk groups (potential super-spreaders) seeks to alleviate this risk. There are also a number of laws that have been on the books many years that make it illegal to intentionally spread disease and force compliance with some public health mandates. These laws and mandates work pretty well considering people with life threatening infections are not too concerned with trouble in the seemingly distant future, or who like Typhoid Mary simply don’t believe they are a threat.

Last but not least, the environment can be a key factor in super-spreading events. Crowding, poor ventilation, improper isolation procedures, unnecessary movement of the infectious, and misdiagnosis have all been identified as factors during the SARS pandemic [1]. For fairly unusual diseases like plague, misdiagnosis is likely to happen frequently in the early phase of an outbreak. Crowding and ventilation are probably significant reasons why ships have been so frequently associated with explosive historic epidemics.  A super-spreading event has already happened before the ship pulls into the dock releasing a new set of super-spreaders in the port. The same could be said for clustering together in buildings during cold weather.

To make things even more complicated, super-spreading goes down the animal chain for zoonotic diseases.  Mosquitoes infected with West Nile Virus preferentially feed on the American Robin, 17 times more likely than by chance in one study [1]. The super-spreading phenomenon could extend to transmission of the pathogen by vectors and among reservoir hosts. Cattle have been documented as being super-spreaders of brucellosis and E. coli O157. In one UK study, 9% of cattle accounted for 96% all bacteria detected in fecal specimens and were high shedders of E. coli O157 [1].

The super-spreading phenomenon is not new but it is only now that our epidemiological models are beginning to seriously wrestle with its implications. These events introduce more uncertainty into our predictions and analyses than we are often comfortable with. We crave certainty in an uncertain world. As difficult as super-spreaders will make the lives of public health professionals preparing for future threats and coping with ongoing outbreaks, they may be the key to understanding many historical mysteries.

References:

[1] Stein RA (2011). Super-spreaders in infectious diseases. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 15 (8) PMID: 21737332

[2] Lloyd-Smith JO, Schreiber SJ, Kopp PE, & Getz WM (2005). Superspreading and the effect of individual variation on disease emergence. Nature, 438 (7066), 355-9 PMID: 16292310

[3] Galvani AP, & May RM (2005). Epidemiology: dimensions of superspreading. Nature, 438 (7066), 293-5 PMID: 16292292

Contagions Round-up 20: Past is Prologue in Science too!

Congratulations to Wonders & Marvels for winning the Cliopatria Award for Best History Group Blog of 2011 and to Lindsey Fitzharris of The Chirurgeon’s Apprentice who won the Cliopatria Award for Best History Individual Blog of 2011. What a year for history of medicine!

Starting with Lindsey’s latest post, let’s get this round-up rolling. The Chirurgenon’s Apprentice started the new year with a post on Cold Like the Dead: Learning Dispassion through Dissection.

Marri Lynn of Wonders and Marvels writes about the many medicinal uses Nicolas of Poland found for snakes.  Elizabeth Fix also of Wonders & Marvels writes about the search for immortality and the Philosopher’s Stone. Adrienne Mayor of Wonders & Marvels tells us that the quest for stem-cell like rejuvenation is ancient indeed!

Eric Michael Johnson of Primate Diaries discusses uses of the past by scientists and science writers.

Caroline Rance of The Quack Doctor reviews Moore’s Shropshire Doctors and Quacks.

Here at Contagions, I looked at a study of malaria in 18th century Finland and the process of retrospective diagnosis today.

Katy Meyers of Bones Don’t Lie looks at malaria trends in the UK and the discovery of brucellosis in medieval Albanian remains.

Kristina Killgrove of Powered by Osteons takes on a recent paper on the plague of Athens in the play Oedipus Rex, shares some material on ethics in bioarchaeology (part 1: Americas), and skeletal evidence of lead poisoning in ancient to medieval Rome.

Maryn McKenna of Superbug has been on the trail of completely resistant TB in India and in Italy.

On the other hand, Vincent Racaniello of The Virology Blog celebrates India’s polio free anniversary, and reassessed the mortality rate of ebolavirus, and discusses the recent moratorium on influenza H5N1 transmission research.

Zoonotica writes about the importance of bovine TB that is causing the planned cull of badgers in Britain.

Tara Smith of Aetiology writes about some of her recent research on MRSA in pork products.

Jennifer Frazer of The Artful Amoeba writes a scary finding on the durability of noravirus (Norwalk virus).

Michael Walsh of Infection Landscapes writes on our ancient passengers the Helminths (worms).

Small Things Considered took a look at what’s so scary about restroom microbiota.

Top 11 in 2011

As the year comes to a close, I thought I would share the top 11 posts here at Contagions for this past year. I’m excluding round-ups and the educational chain of infection posts. These chain of infection posts account for over a third of all page views on this blog over the year and all time! So without further ado, here are the top 11 regular posts based on page view stats as of December 29, 2011.

1. Pandemic Influenza: 1510-2010
2. Beyond Pelusium
3. Did India and China Escape the Black Death?
4. Vampire Prevention in Eighth Century Ireland
5. Rinderpest, Measles and Medieval Emerging Infectious Diseases
6. The Vampire in the Plague Pit
7. Hunting Pathogens in the Siberian Permafrost
8. Plague in 18th century Egypt
9. DNA of the Black Death at East Smithfield, London
10. Plague DNA from Late Antique Bavaria
11. Epidemiology of the Russian Flu, 1889-1890

Happy New Year!!

Contagions Round-up 18: A Load of Links

Over the last week or so I haven’t got a chance to blog as much as I would like. Meanwhile, my reader has been filling up with a load of great links worth sharing.

Ancient and Medieval Life

Tim Clarkson of Senchus asks Where’s the beef? in early Edinburgh.

I wrote about new information on the Staffordshire hoard of gold scrap on Heavenfield.

Guy Halsall of Historian on the Edge shares his latest writing project on the Genesis of the Frankish Aristocracy  in four parts. It would have been helpful to provide links to the other three parts! (part 2, part 3, part 4)

Krystal D’Costa of Anthropology in Practice writes about the use of cock’s crow to keep time in the Middle Ages.

Bamburgh Research Project has posted a report of their re-excavation of Brian Hope-Taylor’s trench at Bamburgh including finding old archaeology placement tags and new finds in the enlarged trench. They were able to confirm occupation of Bamburgh Rock back to neolithic times (5000 years before present).

Jonathan Jarrett of A Corner of Tenth Century Europe has been busy updating us on his trips and conferences, and sometimes a combination thereof like his recent post on Lastingham. He also reviewed Richard Hodges’ Goodbye to the Vikings?

Magistra et Mater wrote an interesting post on slavery viking style.

Thinking of ancient warfare, Adrienne Mayor of the group blog Wonders & Marvels writes of the first chemical agents as ancient crowd control.

William Eamon of the Labrynth of Nature writes about Renaissance astrology and the black pepper markets. Reminds me how my favorite 8th century monk had a pouch of pepper among his meager possessions to pass on to his students at his death.

Book Reviewer extraordinaire Curt Emanuel, the Medieval History Geek, has been blogging up a storm lately. My recent favorite post is The Almanni: A Roman Myth and his latest book review is of The Rhetoric of Power in Late Antiquity.

Kristina Killgrove’s Roman DNA Project has released a post with the project’s goals. And at her blog Powered by Osteons, she writes about differentiating cranial vault deformation from aliens. How about something a little closer to your usual time period? I’d like to know more about cranial vault modification among those pointy headed Huns.

Katy Meyers of Bones Do Not Lie has been busy writing with posts on the practice of Os Resectum, the New World-Old World debate on syphilis, and on using historical texts to retrospectively diagnose disease.

A Contagious Landscape

Marri Lynn on the group blog Wonders & Marvels of the Leper’s Legendary Decay.

I wrote about the evidence (or lack of it) that India and China experienced the Black Death here at Contagions.

Elizabeth Lehfeldt of the group blog Wonders & Marvels writes of female confessors during the Black Death.

Lindsey Fitzharris of the group blog Wonders & Marvels tells us about the use of  “corpse medicine” in early modern England. On her own blog The Chirurigeon’s Apprentice Lindsey writes about bloodletting, leeching and cupping and concepts of what lies beyond the grave in early modern England.

Tara Smith of Aetiology discusses the risks of castrating lambs with your teeth!

Michael Walsh of Infection Landscapes brings us a profile of rotavirus. At his Germscape microblog, he discusses maps of a recent E. coli outbreak and the global spread of hepatitis B and the global spread of chronic hepatitis C.

Flu season is upon us in the northern hemisphere again, so influenza is back in the news. Vincent Racaniello of the Virology Blog writes about a much hyped discovery and experimentation with the lethal avian H5N1 flu virus in ferrets.

Connor Bamford of the Rule of 6ix has also been writing about influenza, wondering where influenza hides in the summer and about dendritic cells acting as Trojan horses for viruses. Connor also hosted the latest edition of the MolBio Carnival.

Finalists for Open Lab 2011 have been announced. Check out some of the best posts of 2011. This list of 51 posts was chosen from over 700 nominated posts for this year.

Whew! This should be enough to keep you reading for a while. Enjoy!