Category Archives: biosecurity

War as a Driver in Tuberculosis Evolution

by Michelle Ziegler

Russia has been all over the news lately. Beyond our recent election, increased Russian activity on the world stage has public health consequences for Europe and farther afield. It has been known for a long time that post-Soviet Russia had and continues to have serious public health problems. One of their particular problems that they have shared with the world is their alarmingly high rate of antibiotic resistant tuberculosis. There is no mystery over the root cause of their antibiotic resistance woes — poor antibiotic stewardship (Garrett, 2000; Bernard et al 2013).

A study by Vegard Eldholm and colleagues that came out this fall sheds light on the origins of particularly virulent tuberculosis strains with high rates of antibiotic resistance that recently entered Europe.  A large outbreak among Afghan refugees and Norwegians in Oslo, Norway, provided a core set of 26 specimens for this study that could be compared with results generated elsewhere in Europe (Eldholm et al, 2010). The Oslo outbreak clearly fits within the Russian clade A group that is concentrated to the east of the Volga River in countries of the former Soviet Union. They name this cluster the Central Asian Clade, noting that it co-localizes with region of origin of migrants carrying the MDR strains of tuberculosis reported in Europe.

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Figure 5. Phylogeny of the Afghan Strain Family (ASF). Colored boxes represent the country of origin: Afghanistan is orange; other countries are gray. (Eldholm et al, 2016)

When the Oslo samples are added to the family tree, phylogeny, of recent tuberculosis isolates from elsewhere in Europe a distinctive pattern emerges. The branches on the family tree are short and dense, suggesting that this is recent diversity, that they calculate to have occurred within approximately the last twenty years (Eldholm et al, 2016).

The Central Asian Clade spread into Afghanistan before drug resistance began to develop, probably during the Soviet-Afghan war (1979-1989) producing the Afghan Strain Diversity clade. Slightly later, the Central Asian Clade still in the former Soviet states begins to accumulate antibiotic resistance as the public health infrastructure crumbles in the wake of the dissolution of the USSR. The invasion of Afghanistan by the US and its allies in 2002 toppled the Afghan state, crippling infrastructure and spurring refugee movements within and out of Afghanistan. The lack of modern public health standards in Afghanistan since their war with the introduction of these strains by the Soviets in the 1980s provided fertile ground for the establishment and diversity of tuberculosis in the country. Instability has been pervasive throughout the entire region sending refugees and economic migrants from both Afghanistan and the former Soviet states into Europe.

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Movements of the Central Asian Clade (CAC) since c. 1960 and the subsequent Afghan Strain Family (ASF). (Eldholm et al, 2016)

Their dating of the last common ancestor for the Central Asian Clade to c. 1961 is significantly younger than the previous dating of 4,415 years before present for the Russian clade A (CC1) of the Beijing lineage of Mycobacteria tuberculosis. They account for this difference by noting differences in their methods of assessing sequence differences and note that their method is in line with other recent evolutionary rates for other tuberculosis clades.  The diagnosis dates and length of the arms on their reconstructed phylogeny suggests that there were multiple, independent introductions of the cases from Afghanistan and the former Soviet republics. This is consistent with a repeated periods of refugee movements from central Asia into Europe.

The rapid proliferation and diversification of the Afghan Strain Family may be explained by a known syndemic between tuberculosis and war (Ostrach & Singer, 2013). Conditions of war everywhere disrupt food systems, destroy critical infrastructures such as electricity and water systems, interrupts medical supplies, and the human public health infrastructure of the country. Malnutrition and stress are known contributors to immune suppression. Many pathogens flourish simultaneously in these conditions increasing the infectious challenges the population must fend off. Diarrheal diseases are the most acute and demanding of rapid attention, allowing longer-term diseases like tuberculosis to slip through the overburdened healthcare system. Afghanistan has experienced nearly forty years of war, political instability, and repeated infrastructure destruction. Thus, they were primed for both the establishment of new tuberculosis strains during the Afghan-Soviet war in the 1980s along with the proliferation and diversification of tuberculosis during the Afghan-American war of the last sixteen years.

Established syndemics between tuberculosis and war have been made retrospectively following the Vietnam war and the Persian Gulf war of 1991 (Ostrach & Singer, 2013). In Vietnam, prolonged malnutrition caused an eruption of tuberculosis along with malaria, leprosy, typhoid, cholera, plague, and parasitic diseases.  A WHO survey in 1976 found that Vietnam had twice the incidence of tuberculosis over all of its neighboring countries (Ostrach & Singer, 2013). When the military intentionally targets water infrastructure as it did in Vietnam and Iraq, the production of civilian infectious disease is a tactic of war. In both Vietnam and post-Gulf war Iraq, more civilians died of malnutrition and infectious disease than enemy soldiers died of all causes (Ostrach & Singler, 2013).

It seems likely that this is just one of the first studies to establish a link between serious infectious disease developments and the Afghan wars. The current war zones throughout central Asia and the Middle East already have ramifications for the public health of the entire world that walls along borders will not be able to stop. Most of the cases in the Oslo outbreak were Norwegians, not Afghan immigrants. Diseases will spread beyond the migrants so country of origin screening will be of little use before long.


Reference

Eldholm, V., Pettersson, J. H. O., Brynildsrud, O. B., Kitchen, A., Rasmussen, E. M., Lillebaek, T., et al. (2016). Armed conflict and population displacement as drivers of the evolution and dispersal of Mycobacterium tuberculosis. Proceedings of the National Academy of Sciences of the United States of America, 201611283–16. http://doi.org/10.1073/pnas.1611283113

Ostrach, B., & Singer, M. C. (2013). Syndemics of War: Malnutrition-Infectious Disease Interactions and the Unintended Health Consequences of Intentional War Policies. Annals of Anthropological Practice, 36(2), 257–273. http://doi.org/10.1111/napa.12003

Bernard, C., Brossier, F., Sougakoff, W., Veziris, N., Frechet-Jachym, M., Metivier, N., et al. (2013). A surge of MDR and XDR tuberculosis in France among patients born in the Former Soviet Union. Euro Surveillance: Bulletin Européen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin, 18(33), 20555.

An Anniversary year for Natural Disasters: 1815, 1665, and 1315

There are major natural disasters every year. In the last year alone we have had the major earthquake in Nepal just in the last couple days and a historic epidemic of Ebola. It’s too soon to tell how these latest disasters will seen by history and effect historical interpretations. This year there are three natural disaster anniversaries that stand out from the rest not just due to their mortality but also because of their impact on how we interpret the past.

Tambora, 1815

Mount Tambora Volcano, Sumbawa Island, Indonesia
Mount Tambora Volcano, NASA image (public domain)
Just a few weeks ago there was a minor splash in the news to mark the 200th anniversary of the eruption of Tambora on April 5, 1815. The photo to the right is the caldera of Tambora taken from space. As tragic as the thousands of deaths directly related to the eruption are, 1815 is best known as the ‘year without a summer’, a volcanic winter. It is impossible to know how many deaths resulted from crop failures and unseasonable weather. As the most recent volcanic winter, 1815 is an important because we have the most reliable scientific data, economic data, and descriptions of the effects on health and culture from people in all walks of life all over the globe. I don’t know as much about Tambora and its after effects as I would like, so I’m planning on reading The Year Without a Summer by historian William Klingman and meteorologist Nicholas Klingman (2013). If I like it, maybe you will hear more about it later this year.


Great Plague of London, 1665

This year is also the 350th anniversary of the Great London Plague that was followed closely by the Great London fire. Despite its reputation, the great plague of London was not the last major plague of Europe by a long shot.

17th century London
17th century London

The 1665 plague of London claimed up to 100,000 lives, about as many as died in the Marseille plague of 1720-3. Fifty years later, a similar size plague struck Moscow under Empress Catherine the Great. Yet, the London Plague is the one that gets the most attention.

A great deal of the notoriety of the Great Plague of London comes from the amount and quality of resources available in English.  Daniel Dafoe immortalized the plague in his novel, Journal of a Plague Year written in 1722. A savvy author, Dafoe timed it to take advantage of plague fears in southern Europe, concurrent with the plague in Marseille. It is testament to the Dafoe’s skill as a writer than his novel is often taken as historical evidence. I think I’ll mark the anniversary by reading Defoe’s classic.

The London plague has also been magnified by it linkage with the great fire of London in 1666. The relationship between the fire and the plague has been controversial. It has been sometimes assumed that the fire ended the plague, but the plague was winding down before the fire began. However, it is likely that the fire removed the environment that had supported the plague preventing its return; over 80% of the citizens of London were left homeless. Restoration of the capital city after the great fire also immortalized 1665-6 in the history of London.


Great European Famine, 1315

A less combustible but perhaps equally deadly anniversary this year is that of the Great Famine of 1315 that effected most of continental Europe. Seven hundred years ago the famine began and, while its hard to estimate famine mortality over three to seven years, perhaps up to 15% of Northern Europeans died. It began with soaking and then flooding rains that destroyed winter crops for two years with yields of wheat and rye in England and Wales 60% below normal in 1316, and again in 1321 with similar drops in yield. Also beginning in 1315 the great bovine pestilence, possibly rinderpest,  begins in Central Europe and spread across the continent: France and Germany, the Low Countries,  Denmark and England by 1319. In just one year, England and Wales lost approximately 62% of all bovines (Slavin 2012). The loss of dairy and beef was compounded by the fact that oxen provided the vast majority of traction and fertilizer. With similar losses across Europe, it took nearly 25 years to return cattle numbers to the pre-epizootic levels.

There was no respite for the 14th century. The childhood survivors of the famine and food shortage were the adults who were cut down by the Black Death in the 1340s. What effect malnutrition had on their developing immune system is a line of inquiry being explored by anthropologists Sharon DeWitte and historian Philip Slavin (2013). Let us not forget, it still got worse, between the crop failures and panzootic of 1315 and the Black Death in 1346 , the Hundred Years’ War begins in 1337.

References

Devaux, C. A. (2013). Small Oversights That Led to the Great Plague of Marseille (1720-1723) Lessons From the Past. Infection, Genetics and Evolution, 14(C), 169–185. doi:10.1016/j.meegid.2012.11.016 (for comparisons to other epidemics)

Slavin, P. (2010). The Crisis of the Fourteenth Century Reassessed: Between Ecology and Institutions — Evidence from England (1310-1350). EHA Paper, 1–14.

Slavin, P. (2012). The Great Bovine Pestilence and its economic and environmental consequences in England and Wales, 1318–501. The Economic History Review, 1–28.

Dewitte, S., & Slavin, P. (2013). Between Famine and Death: England on the Eve of the Black Death—Evidence from Paleoepidemiology and Manorial Accounts. Journal of Interdisciplinary History, 1–25.

Plague in Surat: 20 Years Later

I can’t let 2014 pass in a few weeks without mentioning that this fall was the twentieth anniversary of the plague outbreak in Surat, India — a major turning point in modern plague history and in the development of the (re)emerging infectious disease paradigm.

In the final accounting, 53 people died of plague, mostly pneumonic, but there are over 5000 cases classified as suspected and at least half a million people fled across India. Compared to other pneumonic plague outbreaks in Africa within the last twenty years, the number of deaths was small and the mortality rate tiny (1% of suspected cases). The government response was not only woefully inadequate but also exacerbated the damage within India and scared the rest of the world.

The lessons learned from Surat are really what is important.

  • The need for a national database to keep track of seemingly isolated cases and the need for surveillance of rodents, even when there haven’t been any human cases in many years. Better surveillance established since 1994 has identified several more plague outbreaks in India and enough evidence of enduring plague foci in the country.
  • The need for transparency, willingness to accept foreign help and the futility of trying to hide the epidemic from the press.
  • The costs of unsupported allegations of biological warfare or terrorism are too high to make unless there is certainty. It ultimately does not deflect responsibility away from the government for the response. The political costs for governments who make official erroneous allegations are greater than accepting responsibility for the outbreak.

In this month’s issue of the Indian Journal of Microbiology, the full genomic sequence of Yersinia pestis collected at Surat in 1994 and at a 2002 outbreak in India was released. Four samples were sequenced and they are all four different strains. Unfortunately, they did not do a phylogenetic analysis to indicate where they fit on the Y. pestis tree.

Twenty years ago it was the double hit of plague in Surat in 1994 and the discovery of antibiotic resistant plague in Madagascar in 1995 that raised concern about re-emerging infection diseases. Antibiotic resistant strains of Yersinia pestis have continued to appear in Madagascar and now insecticide resistant fleas are a problem as well. While public health processes and surveillance are better than in 1994, there has been no improvement plague incidence or concerning resistant strains.

Ebola is currently extracting the toll that was feared of plague in Surat two decades ago. If Surat was the warning that acute pandemics are still possible, Ebola is showing how far we still have to go 20 years later. Both plague in Surat and Ebola in 2014 are also reminding us that knowing what to do to stop an epidemic is not enough, execution is everything.

Further reading on Surat:

Barrett, Ron. (2008) “The 1994 Plague in Western India: Human Ecology and the Risks of Misattribution” p. 49-71 in Terrorism, War, or Disease? Unraveling the Use of Biological Weapons. Edited by A.L. Clunan, P.B. Lavoy, and S. B. Martin. Stanford Security Studies. Stanford University Press. This is the best analysis of the Surat outbreak that I have found.

Ziegler, Michelle (2014) The Black Death and the Future of the Plague. The Medieval Globe, 1: 183-199 for an overview of plague since 1994.

Mahale, K. N., Paranjape, P. S., Marathe, N. P., Dhotre, D. P., Chowdhury, S., Shetty, S. A., et al. (2014). Draft Genome Sequences of Yersinia pestis Strains from the 1994 Plague Epidemic of Surat and 2002 Shimla Outbreak in India. Indian Journal of Microbiology, 54(4), 480–482. doi:10.1007/s12088-014-0475-7

For more on antibiotic resistant plague, see this past post and on the most recent reported pneumonic plague outbreak in Madagascar.