Friday, April 08, 2011

Tuberculosis, Canadian first nations, and pandemics

Over at my blog, I linked to a startling news item pointing to the Proceedings of the National Academy of Science paper "Dispersal of Mycobacterium tuberculosis via the Canadian fur trade". The abstract?

Patterns of gene flow can have marked effects on the evolution of populations. To better understand the migration dynamics of Mycobacterium tuberculosis, we studied genetic data from European M. tuberculosis lineages currently circulating in Aboriginal and French Canadian communities. A single M. tuberculosis lineage, characterized by the DS6Quebec genomic deletion, is at highest frequency among Aboriginal populations in Ontario, Saskatchewan, and Alberta; this bacterial lineage is also dominant among tuberculosis (TB) cases in French Canadians resident in Quebec. Substantial contact between these human populations is limited to a specific historical era (1710–1870), during which individuals from these populations met to barter furs. Statistical analyses of extant M. tuberculosis minisatellite data are consistent with Quebec as a source population for M. tuberculosis gene flow into Aboriginal populations during the fur trade era. Historical and genetic analyses suggest that tiny M. tuberculosis populations persisted for ∼100 y among indigenous populations and subsequently expanded in the late 19th century after environmental changes favoring the pathogen. Our study suggests that spread of TB can occur by two asynchronous processes: (i) dispersal of M. tuberculosis by minimal numbers of human migrants, during which small pathogen populations are sustained by ongoing migration and slow disease dynamics, and (ii) expansion of the M. tuberculosis population facilitated by shifts in host ecology. If generalizable, these migration dynamics can help explain the low DNA sequence diversity observed among isolates of M. tuberculosis and the difficulties in global elimination of tuberculosis, as small, widely dispersed pathogen populations are difficult both to detect and to eradicate.

This finding documents any number of things, such as the underlying and continuing vulnerability of Canada's indigenous peoples to epidemic disease, the long-standing ties between French Canadians--then, as commenters at CBC point out, simply Canadiens--and First Nations, the highly contingent nature of the transmission of pandemic diseases, and the extent to which these pandemics can remain below public attention for decades or even centuries. Parallels with the the evolution and spread of HIV, reconstructed from fossil viruses and genetic data, are entirely merited.

The data point to 1908 as the year that HIV group M (which now infects more than 31 million people worldwide) began its assault — somewhat earlier than the previous best estimate of 1931. Though 1908 is an approximation, the evidence suggests that the true date almost certainly falls sometime between 1884 and 1924.

When such evolutionary studies are overlaid with the history of human societies in Africa, a detailed picture of the origins of HIV group M comes into focus. Historically, chimpanzees in west-central Africa have been hunted for food. Many of them are also infected with the virus that HIV evolved from, Simian Immunodeficiency Virus (SIV). Butchering chimps probably repeatedly exposed local hunters to SIV. The virus may have made the leap to infect people many times — but only at the turn of the century did this viral invasion gain a foothold in the population. Around that time, a hunter seems to have picked up the virus from a chimp in the southeast corner of Cameroon and carried the pathogen along the main route out of the forest at the time, the Sangha river, to Leopoldville (modern-day Kinshasa). Mirroring the growth of the cities in Africa, the virus spread slowly in Leopoldville until around 1950, when it began to proliferate rapidly. Still undetected, the virus continued to evolve and to diversify, leapfrogging through burgeoning cities. With the increasing ease of global travel, HIV was carried out of Africa and around the world — and the rest, as they say, is history.

This reconstruction of HIV's origins certainly satisfies our curiosity — but it also serves as a practical reminder of the conditions that foster the emergence of new diseases. We cannot stop evolution. Pathogens regularly make the leap to infect new hosts, and we increase our chances of being victimized by one of these host switches, when we take on lifestyles that put us in close contact with other species — especially ones closely related to us — like chimpanzees. The early history of HIV also illustrates that the virus is not invincible. For more than 50 years, HIV infected human populations but had such a small impact that it wasn't noticed against the backdrop of other diseases. In comparison to pathogens like malaria (which is carried by mosquitoes) and the common cold (which can travel through the air), HIV is pretty terrible at getting from one person to the next, relying on the direct transfer of body fluids. The virus only got its start in humans through a confluence of opportunity and history — the practice of hunting chimpanzees, the rise of densely populated cities in Africa, and a correlated increase in high-risk behaviors involving the exchange of body fluids (e.g., injection drug use, prostitution). The fact that changes in human societies were so critical in the rise of the virus suggests that changes in human societies could snuff it as well.

The lead author notes that in the case of tuberculosis, isolated early cases produced an epidemic only when living conditions deteriorated sharply from the late 19th century on, as traditional lands were confiscated, children sent to residential schools, and living conditions on reserve became--and remained--Third World. If these conditions didn't occur, then presumably tuberculosis would be much less of a problem on Canada's reserves.


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