Wednesday 1 March 2017

A Revised History of the African Trypanosomes

                                                     

Human African trypanosomiasis (HAT), or African sleeping sickness, was a smoldering disease before European colonization of the African continent. The famous American explorer Henry Morton Stanley has been blamed for spreading it across the tse tse belt of Africa from west to east in the late 1800s, setting off a series of epidemics that have killed millions and continue to this day. Similarly, nagana, the related disease in animals has prevented the rearing of livestock in the tse tse belt.


The tse tse belt of Africa. Trypanosoma brucei and the tse tse
fly are confined to this region. Image by Mba123; CC BY-SA 3.0
The tse tse belt, named for the blood sucking fly that inhabits its ecosystems, is pivotal in the history of the parasite. Trypanosoma brucei must complete part of its life cycle in the fly and the fly cannot live outside the tse tse belt; therefore, the parasite cannot either. Early theories suggested that the trypanosomes were originally parasites of insects that later invaded vertebrate hosts when the insects began feeding on blood.

African sleeping sickness is caused by subspecies of a protozoan parasite, Trypanosoma brucei. In his book Forgotten People, Forgotten Diseases, Peter J. Hotez sums up the long-accepted breakdown of the species: “T. brucei gambiense (T. b. gambiense) is the cause of human sleeping sickness in West Africa.... T. brucei rhodesiense (T. b. rhodesiense) causes HAT in East Africa.... A third subspecies, T. brucei brucei (T. b. brucei), does not infect humans.” Trypanosoma b. gambiense, we are told, does not infect animals. Trypanosoma b. rhodesiense infects both animals and humans. Trypanosoma b. brucei is death to domestic livestock.

Untreated, HAT is almost invariably fatal. Trypanosoma b. rhodesiense acts quickly, invading the central nervous system and bringing death within months. Trypanosoma b. gambiense causes a more chronic illness that can last for years. Because of this relatively milder course of disease, and because T. b. gambiense is said to infect only humans, it has been theorized that we have had it for much longer and are better adapted to it.

Much of this is probably wrong.

Where Did African Sleeping Sickness Come From?



This tse tse fly is in the collection of the
American Museum of Natural History.
Image by Tam Nguyen. CC BY-SA 3.0

Today, genetic studies tell us that the African trypanosomes evolved in Africa, having diverged from T. cruzi, the agent of South American tryanosomiasis. Stevens et al date this divergence to about 100 million years ago, when the two continents separated. They write that the most likely scenario is that the ancient ancestors of these species were parasites of small early mammals, and later adapted to larger animals and the tse tse fly vector.

According to Stevens et al the ancestors of today's pigs and hippopotamuses were predominant in Africa until about 23 million years ago. “It is interesting,” they write “that several present-day trypanosome species are specific to pigs... and that analysis of tsetse blood meals indicates suids [pigs] to be a favourite food source.... The ecological requirements of tsetse and pigs (forest and thickets) are also very similar.” Perhaps HAT was a long-time disease of pigs that jumped to humans.

Investigators have found T. b. gambiense in various wild and domestic animals in the tse tse belt. Macleod et al, however, write that “the principal reservoir host for T. b. gambiense appears to be the domestic pig.” These findings lend further support to the idea that pigs may have been host to the parasite for thousands of years before humans were, and challenges the long-held belief that T. b. gambiense is an exclusively human parasite.

Subspecies of Trypanosoma brucei


Modern genetic analysis has revealed much about T. brucei. According to Balmer et al, the subspecies T. b. rhodesiense probably doesn't actually exist; rather, populations infective to humans are apparently populations of T. b. brucei that have acquired the serum resistance associated gene (SRA). Evidence suggests that this genetic mutation has evolved more than once and can be passed from one T. b. brucei population to another.

Meanwhile, T. b. gambiense apparently evolved resistance separately and shows less genetic diversity than T. b. brucei, suggesting that it infected humans and spread relatively recently. This again contradicts the idea that the subspecies has had a longer association with humans, which brings us back to the explorer Henry Morton Stanley.

Stanley and the Spread of African Sleeping Sickness



A map showing the main slave trade routes in Medieval times.
Runehelmet derived from Aliesin. CC BY-SA 3.0
Balmer et al don't suggest how recently T. b. gambiense might have spread, or where it started from. We know that HAT was present in northern Africa centuries before Stanley's expeditions: Arab slave traders from the 14th century left accounts of African slaves with typical symptoms. As well, Roberts and Janovy write that “swollen [lymph] nodes at the base of the skull were recognized by [European] slave traders as signs of certain death, and slaves who developed them were routinely thrown overboard...”

It appears, however, that HAT was not widespread in the tsetse belt, or at least it took few lives until after Stanley established shipping routes on the Congo River and helped the avaricious and brutal King Leopold II of Belgium to exploit the people and resources of what became the Congo Free State. If Stanley's exploits were the first steps toward epidemic HAT in the tsetse belt, Leopold's virtual genocide likely ensured that spreading trypanosomes upriver in human bloodstreams would precipitate disaster (even today, poverty and war in the tse tse belt bring epidemics of sleeping sickness).

 Stanley's last expedition started from the mouth of the Congo in 1887 and lasted about a year, but a 1904 New York Times article dates the beginnings of the HAT epidemic to about a decade after Stanley: “About six years ago,” the article states, “missionaries on the Congo began to write home of a mysterious disease which was ascending the river.” It was a wave of disease that would be “sure death to every person attacked by it.”
 

Further Reading About the History of African Trypanosomes


Alsan, M. (2012) "The Effect of the TseTse Fly on African Development." (2012)

Balmer O, Beadell JS. (2011) "Phylogeography and Taxonomy of Trypanosoma brucei." PLOS Neglected Tropical Diseases 5:2

Baumeister RF, and Tierney J. (2012) "Henry Morton Stanley's Unbreakable Will." Smithsonian.com Adapted from Willpower, by Roy F. Baumeister and John Tierney.
 
Cordon-Obras C, Berzosa P. et al. (2009) "Trypanosoma brucei gambiense in domestic livestock of Kogo and Mbini foci (Equatorial Guinea)." Tropical Medicine & International Health
14:5 535-541 doi:10.1111/j.1365-3156.2009.02271.x

Hoare CA. (1972) The Trypanosomes of Mammals. Blackwell, Oxford.

Hotez PJ. (2007) Forgotten People, Forgotten Places. Washington, DC: ASM Press

MacLeod A, Tait A et al. (2001) "The Population Genetics of Trypanosoma brucei and the origin of human infectivity." Philosophical Transactions of the Royal Society London 356, 1035-1044.

Yale University Genocide Studies Program. "Congo Free State 1885 – 1908." Yale University Genocide Studies Program. Accessed March, 2017.

Stevens JR, Noyes HA et al. (1999) "The Ancient and Divergent Origins of the Human Pathogenic trypanosomes, Trypanosoma brucei and T. cruzi." Parasitology 118: 107-116

Steverding D. (2008) "The History of African Trypanosomiasis." Parasites and Vectors 1:3

The New York Times. (1904) "Tens of Thousands Killed by a Tiny Fly." SM2

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