Chapter
2
One
Millionth Of A Metre
I
didn’t know this until I watched a BBC television documentary a few years ago
called The Private Life Of Plants; but lichen – the patches of variously
shaded matter that grow on gravestones, roof tiles and paving slabs – are not
individual organisms, but a combination of algae and fungi. They function in a
tightly woven, lifelong embrace from which neither can ever escape; nor would
they want to, because neither could survive independently any more. This is
called endosymbiosis. The alga provides the food energy, created through
photosynthesis, and the fungus the protection to see the joint organism through
the harshest of conditions. There are lichens that exist (I hesitate to use the
word “thrive”) in Antarctica[i]
where, incredibly, they manage to carry out photosynthesis at temperatures as
low as -24°C. An organism that exists in near stasis for most of the year, and
below freezing conditions all year round still manages to have a net benefit on
the planet by consuming carbon dioxide and producing oxygen.
Imagine
if, rather than independent beings that could pick and choose what we ate and
what we surrounded ourselves with, humans had an endosymbiotic relationship with
another organism. How would it feel to be part of another organism, or have
organisms living inside you, doing work without which you would die?
Say
hello to your mitochondria. Don’t be shy, they won’t answer back – they
are far too busy converting amino acids and sugars into energy for your cells to
use. Tucked away within the cells of, probably, all animals, mitochondria are
effectively the “boiler rooms” of your cells; yet they didn’t evolve like
the majority of the components of your body, gradually changing or adapting
their functions to suit their host organism, instead the mitochondria
“hijacked” specific types of bacteria and used them in order to extract
oxygen from surrounding molecules[ii].
It may be that such bacterial entities are being used in other parts of cells as
well, which seems to make a mockery of how we view evolution overall – could
it be that large organisms evolved by using other life-forms to give them a head
start? We simply don’t know enough about these processes to say for sure;
however we do know enough to make some people feel rather queasy.
Consider
your gut. Approximately six metres of grey and green muscle and mucous membrane,
which ensures that the nutrients from the food you eat are absorbed correctly
into your body, and the waste that your body doesn’t need is expelled in a
similarly efficient manner. It seems that a day doesn’t pass without a
newspaper, television or magazine advertisement telling people that they should
keep their internal “flora” intact. What a horrible thought – it conjures
up images of delicate fronds of algae and other plant matter gently waving as
the intestinal juices flow past. On a bad day the images are more akin to the
giant orange fungus that exploded out of the body cavities of scientists working
in the crater of a volcano during an episode of the X Files.
Distressingly,
it is the latter image that the yoghurt advertisements are closer to. The many
forms of fungi and “bad” bacteria that threaten to make our digestive
experience an unpleasant one are not alone. A recent study on the nature of
micro-organisms in the human body[iii],
found that most of the individual cells in our body do not, in fact, belong to
our bodies at all, they consist of myriad fungi, bacteria and viruses (viruses
are not really cells, but you get the idea) so numerous that, “because our
bodies are made of only some several trillion human cells, we are somewhat
outnumbered by the aliens.”[iv]
What
Are Bacteria?
If you
divided all definite forms of life into “bacteria” and “everything else”
you would still have far more life in the former group than the latter.
Everything teems with bacteria – sterilization is just a temporary respite:
they will come back, relentlessly, so long as there is something from which they
can obtain nutrients. Obviously, bacteria are extremely small; typically they
are about one micrometre in length – meaning you could fit hundreds of them
end to end in the width of a human hair – although they can be as “large”
as half a millimetre.
The
main difference between bacteria (including the very ancient and robust types,
known as Archaea) and other forms of life is that bacteria don’t have a
nucleus in their one cell. Other single-celled organisms, such as amoebas, do
have a nucleus, which puts them in the same group of life as all other
non-bacterial organisms. The lack of a nucleus means that the bacterium’s[v]
genetic material is in close contact with the rest of the organism’s
components, such as those which convert food into energy. This makes a bacterium
more vulnerable to attack and change, but on the plus side the simpler structure
means that less energy and time is required for it to reproduce.
The
reproduction process for bacteria is without emotion and turmoil: they simply
divide when they reach a certain size. If you consider that there is a marine
bacterium called Pseudomonas Natriegens that can produce another
generation in just under ten minutes[vi]
and that within one day a single bacterium (not a pair, we are talking asexual
reproduction here) could become…well I started working this out, and by 6
o’clock in the morning the number had already reached 68,700,000,000
individual organisms, and I realised that there was not enough room on Earth to
accommodate one day of this single rapidly reproducing specimen! Compare this to
the mosquitoes in Chapter One, which reproduced fully in fourteen days under
ideal conditions, and you get an idea of the kinds of things we are dealing
with. Obviously the world would just be a mass of grey goo if bacteria could
multiply according to their habit but, fortunately for us, most bacteria are heterotrophs,
meaning they cannot make their own food. When their food runs out, the bacteria
cannot multiply.
Like
all tiny things, we have absolutely no idea how many different bacteria there
are in the world. The likelihood is that because of their fragile genetic
protection there are different kinds of bacteria being created faster than we
could ever hope to count them. Certainly most hospitals struggle to keep up with
the mutations that take place within their walls such that a single outbreak of
a new antibiotic-resistant strain is cause for a national emergency. The human
body copes admirably with its own harvest of integrated and not so integrated
bacteria for the most part. When we lose control, though, then we really lose
it.
The
phrase “flesh eating bug” may have been a newspaper seller for a short
period in the early 1990s, but the bacteria that cause Necrotizing Fasciitis
have always been with us, and will remain with us forever. If you have ever had
a severe sore throat, then that will probably have been the result of a form of Streptococcus
bacteria; hence the term “strep throat”. In the vast majority of cases time,
rest and if necessary, a course of antibiotics will deal with strep throat. If
the Streptococcus bacteria responsible for strep throat enters a wound on the
skin, that can lead to something far worse. Eric Cornell, physics Nobel
laureate, takes up the story:
On Oct.
24, 2004, I came down with what I thought were flu symptoms—fever and a sense
of malaise. The next day, I developed an aching pain in my shoulder. The pain
steadily got worse and on Oct. 27, I was referred to the emergency room at
Boulder Community Hospital. There I was diagnosed with necrotizing fasciitis and
I underwent operations to cut away infected flesh, including amputation of my
left arm and shoulder. However, even so, the infection continued to spread and I
was very near death. In the afternoon of Oct. 28, I was airlifted to the Burn
Intensive Care Unit at the University of Colorado Hospital in Denver. Two more
operations removed more skin, muscle, and subcutaneous fat from large areas of
my left torso.[vii]
Professor
Cornell survived his ordeal, after a three week coma and intensive therapy.
Others do not. Fatality rates, according to the US Centers for Disease Control
are around 25 percent, extremely high for an infectious disease. The number of
deaths each year from necrotizing fasciitis is probably around 150,000 to
200,000[viii]
– far less than the annual total for influenza, but a lot more deadly.
Nevertheless, it pales into insignificance when you consider the overall number
of deaths that result from bacterial infections, both directly and indirectly.
Direct
Killers
As a
fourteen-year-old school student, I remember the little needles, the tiny sharp
bunch of concentric spikes that pierced my skin with a click. Phew! That’s
over. But it wasn’t, because like most of my friends, I didn’t have the
right antibodies, meaning that I had never had the disease before, had never
been vaccinated before, or didn’t have natural immunity to the infection. The
second needle was longer. A prefect held me, with my left arm down at my side,
while the nurse inserted the metal spike into my upper arm and filled a void
under the skin with milky-white fluid. A synthetic blister, the legacy of which
is still with almost every person who went to school in the UK up to the mid
1990s, as a small scar.
Vaccinations
don’t always work. The BCG vaccination, named after its French inventors
(hence Bacillus Calmette-Guérin), protects against some types of Tuberculosis,
but not others. The most common and most infectious type – pulmonary
tuberculosis – is poorly controlled by BCG, but for the moment BCG is the best
vaccine widely available. Unfortunately, TB is a widespread and devastating
killer with an average of 1.7 million reported deaths a year between 1995 and
2005[ix]:
and one-third of the world’s population thought to be latently infected with
the bacteria[x]
The reason for the endemic presence of TB is likely to be related to its long
history as a human pathogen. Of the 85 mummies exhumed from a number of tombs in
Egypt, 25 were found to have probably been infected with tuberculosis, with
another twelve definitely infected[xi].
The specimens from the oldest of the tombs showed that even 4000 years ago, the
infection had been caught from other humans rather than (as previously thought)
cattle.
Given
the length of time that humans have had to adapt to the TB bacterium in its
various forms, it is not surprising that most carriers do not actually contract
the disease; but given its reputation as the most deadly infectious disease on
Earth, it has to be taken seriously. Africa is the heartland for TB: Zambia had
118 TB deaths per 100,000 people in 2005 (down from 208 in 1999, but still over
five percent of all deaths); 140 people out of every 100,000 died in Kenya in
the same year from TB (13 percent of all deaths); and in Swaziland in 2005, TB
accounted for 304 deaths per 100,000 people, or ten percent of its already
terrible death rate. Overall rates are dropping because of better health
education along with more widespread vaccination and antibiotic availability,
but the killer still lies dormant, only needing a little nudge to wake it up and
wreak further havoc.
That
nudge may come in the form of global warming.
Bacteria
love heat. Bacteria need heat, and some thrive in conditions that would be
deadly to any other life form. Pyrodictyum grows best at 105 degrees
centigrade, while others cannot reproduce if their temperature drops to less
than 80°C. Truly creatures of Hades[xii].
These “extremophiles” may occupy niches in which no other organism has a
chance of survival, but the majority of bacteria have very specific temperature
requirements well within the realms of humans. Speaking to Martin Wiselka of the
Nuffield Hospital, Leicester, it becomes clear that our heating world will
increasingly become a haven for many types of harmful bacteria. He says: “Most
bacteria which are pathogenic to humans survive and reproduce optimally at
around 37°C (in other words, they are adapted to humans). Bacteria maintained
at this temperature are likely to grow faster and become more infectious than
those at a lower temperature which is why we refrigerate our food to make it
last longer. Certain bacteria will only survive in warm climates.”[xiii]
The
relationship between the growth rate of bacteria and temperature is remarkably
consistent, such that it is possible for scientists to develop general rules to
predict how quickly a specific type of bacteria will multiply depending on
temperature. For example, if a certain type of bacteria doubles in number every
fifteen minutes under a certain set of conditions, e.g. in a test tube full of
milk at 10°C, then under the same conditions but at 15°C the growth rate of
that strain of bacteria can be very accurately predicted. David Ratkowsky and
his colleagues at the University of Tasmania found the relationship held true in
their own samples and the twenty-nine other examples they extracted from various
pieces of scientific literature[xiv].
In short, under ideal conditions, for every five degree increase in temperature,
bacteria divide between 50 percent and 100 percent faster. A mere one degree
increase can therefore increase the division rate of bacteria by around twenty
percent. For a common pathogen like Salmonella (1.4 million cases per
year in the USA[xv]),
this kind of change is vital when working out the time that food can be kept out
of cold storage, and also how many people are likely to be infected under a
range of conditions. Salmonella is not just responsible for the illness caused
by undercooked meat and eggs though: serious as these strains can be, others
have an even darker side.
Typhoid
fever is cause by the bacteria Salmonella Typhi, and is the cause of over
half a million deaths worldwide every year[xvi].
Unlike tuberculosis, typhoid will happily live outside of the body, specialising
particularly in standing water containing human sewage. A pond, well or ditch
only has to contain a fragment of faecal matter from the unwashed hands of a
child for the entire water source to become infected, and the warmer the water
is, the faster it will become infected until every person drinking that water is
bound to ingest the bacteria. Vaccinations are an effective preventative measure
against typhoid and antibiotics can bring most cases under control, but studies
carried out in Vietnam and throughout Africa have found numerous strains of
antibiotic resistant typhoid throughout the population, and even bacteria that
appear to be changing the way that they evolve in order to survive[xvii].
As I discussed in Chapter One, the increased density and mobility of humans is
also creating the conditions for bacteria to mutate more rapidly:
In 1989,
multidrug resistant S. Typhi appeared, with the emergence of strains resistant
to chloramphenicol, ampicillin, trimethoprim, streptomycin, sulfonamides, and
tetracycline. The prevalence of multidrug-resistant S. Typhi has also increased
among travelers. The rate of multidrug-resistant S. Typhi infection in American
travelers acquired in India increased from 30% in 1990–1994 to 35% in
1996–1997, and 4 of 5 travelers with typhoid fever acquired in Vietnam were
infected with multidrug-resistant strains.[xviii]
Not
only are most antibiotics useless against the newest strains of typhoid, it also
won’t be long before, as with influenza, vaccines themselves have to be
updated regularly in order for them to be effective against the disease. With
the Earth due to heat up by another 1.3 degrees centigrade by the middle of the
twenty-first century – twice as much heating as experienced in the last 200
years – we can confidently overlay the heating effect upon the dual
microbiological horrors of overcrowding and excessive travel. Before we look at
the indirect effects of temperature increase, I want you to stop for a few
moments and imagine what that will do to the activity of our bacterial
colleagues.
How do
you feel? Let’s go on.
Indirect
Killers
Like any
good horror story, sometimes you need a bit of comedy to give your mind a rest
from the constant torment it is suffering. I read the war diaries of the unique
and sadly missed comedy genius Spike Milligan over and over again when I was in
my twenties. Such was his skill as a writer; you could be lifted straight out of
a terrible battle scene into a nugget of sparkling wit barely having time to
draw breath. Never forget that you always have time to laugh – it really helps
when contemplating annihilation.
One
moment that has stayed with me concerned the outbreak of pubic lice, or
“crabs” amongst the cable laying team which Spike’s best friend, Harry
Edgington, was part of. Their work was relentless, repetitive and filthy. As
Harry said: “We hadn’t had our clothes off for some considerable time, much
less our underwear, and a bath was only something we vaguely remembered from
long ago.”[xix]
He then goes on to tell in vivid but hilarious detail of how the British army
dealt with such an outbreak – modesty and a low pain threshold are two
attributes that wouldn’t have held the soldiers in good stead. Pubic lice
certainly qualify as a considerable irritation and, like most personal problems
are a ripe target for comedians. Another form of lice-borne disease is, at first
sight, perhaps less prone to having the mickey taken out of it – but then I
remembered an episode of The Simpsons[xx],
part of which went like this:
Miss
Hoover: [shakily] Children, I won't be staying long. I just came from the
doctor, and I have lyme disease. Principal Skinner will run the class until a
substitute arrives.
Ralph:
What's lyme disease?
Pr.
Skinner: I'll field that one. [goes
to blackboard] Lyme disease is
spread by small parasites called ‘ticks’.
[writes ‘TICKS’ on blackboard] When a diseased tick attaches itself
to you, it begins sucking your blood...
Miss
Hoover: [not calmed] Oh...
Pr.
Skinner: Malignant spirochetes infect your bloodstream, eventually spreading
to your spinal fluid and on into the brain.
Miss
Hoover: The brain!? Oh, dear God...
Class:
Wow!
Do I
have to apologise for finding that funny? Ok, sorry if you or anyone you know
has ever had Lyme Disease, I couldn’t help it. Lyme Disease is a very
serious illness if left untreated, causing heart problems and a variety of
nervous conditions, but is very rarely fatal. As a major risk factor, Lyme
Disease is not something that should worry most people. But it is an important
indicator.
Lyme
Disease in the USA is carried by black-footed or deer ticks, which in turn are
carried (or “hosted”) by deer, mice, squirrels and other rodents. In Europe
and northern Asia, other ticks, including the castor bean and sheep tick,
harbour the bacteria that are then passed onto humans and other animals through
their bites. These ticks are hosted by a variety of animals. Ticks, lice, fleas
and other arthropods are sensitive to temperature and other environmental
conditions, including moisture,
habitat type and the availability of hosts, but they cannot migrate on their
own, relying instead on their hosts to move for them.
Figure 3 : Deer Tick (Source: Wikipedia Commons)
As I have said, Lyme Disease is not a serious threat to life, but it has been on
the increase in the USA, steadily growing from less than 10,000 cases in 1991 to
23,000 in 2005[xxi].
This is partly due to better reporting methods, but also the intrusion of humans
into the native habitats (mainly woodlands) of the ticks and their hosts. This
bears a striking resemblance to the way that Ebola has spread in central Africa.
There is also good evidence to show that as humans degrade the habitats they
intrude upon they reduce the number of different species in that habitat – its
“biodiversity” – and thus the competition for food also reduces. The
outcome of this is that one species tends to dominate, and in the case of the
woodlands of north east USA, that is the white-footed mouse[xxii].
The white-footed mouse hosts the deer tick, and the deer tick can infect people
more easily due to the invasive habits of the mouse.
Some
insects carry Lyme Disease; others carry Bubonic Plague. You would be forgiven,
if you live in the Western industrial world, for thinking that plague was just a
bad memory from the past that, thankfully, no longer threatens lives. Sadly,
plague is most certainly alive and well, and is living in Africa: “Globally,
the number of cases of human plague has remained stable from year to year and,
in comparison with other infectious pathologies, can be considered weak.
Nevertheless, human plague remains a public health problem worldwide. The
re-emergence of human plague in Algeria in 2003, fifty years after its last
occurrence further demonstrates that the geographical distribution of natural
foci is not immutable.”[xxiii]
In other words, plague is out there, and it could emerge anywhere.
But
bacteria don’t even need to infect humans to affect them.
The
majority of people on Earth drink milk or eat dairy products. A sizeable
minority eat meat products from cattle, and this proportion is growing as people
in newly industrialised countries start to see the “Western” meat-rich diet
as a symbol of decadence and success. Such a diet is actively promoted by the
meat processing and producing industry throughout the world, partly because many
people in the most industrialised nations are reducing their meat and dairy
intake. Approximately fifteen percent of global calories derive directly from
the consumption of meat[xxiv],
of which a quarter is from cattle. In addition, a significant chunk of the
world’s total calories comes from dairy products. A major cattle disease would
be tragic for those who have become accustomed to a cattle-dependent diet.
Cattle
farmers in tropical and subtropical regions fear the deadly and debilitating
disease Cattle Anaplasmosis, but have to accept it as a known hazard for their
herds. Such is the threat of this disease to commerce, that as far back as 1906
the US government carried out a complete eradication of the disease and placed
strict quarantine measures on its borders to ensure no infected cattle could
cross into the USA from Mexico. The potential of the disease is truly momentous.
Back in 1981 the United Nations Food and Agricultural Organization (FAO) stated:
“The figure must be staggering. Mortality rates range from five percent in
some herds where the disease has been prevalent for many years to as high as
seventy percent during severe outbreaks in herds where the disease has not
occurred previously. Though death losses are sometimes overwhelming, they can
also be minor as compared with weight, milk, and calf losses among surviving
cattle.”[xxv]
Current reports suggest that the disease is still endemic in tropical areas and
will readily infect, and kill any cattle that are introduced alongside immune
animals.
The
most deadly form of cattle anaplasmosis is caused by the bacterium Anaplasma
marginale and most commonly carried from animal to animal by the tropical
cattle tick Boophilus microplus. This tick is, like all ticks, sensitive
to environmental conditions[xxvi],
and will not lay eggs in temperatures of less than 15-20°C. As with mosquitoes
and midges, a small rise in regional temperature will allow the ticks to breed
further north, at a higher altitude and potentially on animals that have not
been able to host them in cooler temperatures. If a disease with the virulence
of cattle anaplasmosis appeared in humans then we would be considering a
pandemic on the scale of the 1918 influenza outbreak, or the aforementioned
bubonic plague. Interestingly, the bacteria that are readily spread by the
tropical cattle tick to cause cattle anaplasmosis is of the same Genus[xxvii]
as the bacteria that is spread by the deer tick to cause the potentially lethal
human form of anaplasmosis. The more you look into it, the more complex the web
becomes.
Typhus
is nothing to do with typhoid. The two are often confused, and both are caused
by bacteria: but whereas typhoid fever is spread via infected watercourses,
typhus is most usually carried by the human body louse, spreading the bacteria
via its faeces being scratched into a louse bite. Typhus is at its worst when it
causes epidemics of disease; typically where sanitary conditions are poor,
clothes are rarely changed and floor coverings and furnishings filthy. Such
conditions prevail during wartime, in prison camps, ghettos, trenches,
concentration camps – the physical and mental brutality carried out by the
guards in the Nazi concentration camps of World War II is only part of the tale:
Maj.
William A. Davis, MC, while serving as liaison officer from the U.S.A. Typhus
Commission to the 21st Army Group, recorded the typhus fever epidemic that
occurred at the Belsen Concentration Camp, Belsen, Germany. This camp was taken
by the British Second Army on 15 April 1945. Among the 61,000 inhabitants, there
was widespread suffering from starvation, typhus, dysentery, tuberculosis, and
other diseases. Typhus had been prevalent in the camp for 4 months, and there
were approximately 3,500 cases at the time of liberation. Practically all of the
internees were heavily infested with lice.[xxviii]
At the
start of World War I, Serbia was literally decimated by typhus, killing 200,000
of its people. Worse was to come; after cutting through much of the eastern war
front in Europe, it ravaged post-war Russia, killing around ten million people
with a fifty percent fatality rate[xxix].
War stories are awash not only with experiences of awful living conditions, but
also of delousing: the use of toxic powders and other chemicals, including DDT;
hair being forcibly shaved off; clothing and blankets being burnt. These methods
were often brutal and always uncomfortable, but generally the only rapid way to
prevent disease epidemics in such conditions.
The
kinds of conditions that much of the world’s population has to put up with are
creating new breeding grounds for diseases like typhus. The cramped, unserviced
slums skirting Mumbai, Sao Paolo and Jakarta are barely acknowledged by the same
authorities that pride themselves on their city’s economic opportunities.
These shanty-towns, favelas and ghettos are the result of the aspirations that
existed in the minds of travellers in search of economic wealth; aspirations
that never came to fruition because the dream-sellers failed to deliver on their
promises. Instead, the aspirant slum-dwellers get disease and a way of life that
is often far worse than the one they wanted to escape from.
Most
poignant of all, the bacteria that cause these explosive diseases are almost
certainly the same kind of bacteria that first found their homes in our cells
millions of years ago[xxx].
In a striking example of the wheel of life turning full circle, the
mitochondrial bacteria that we rely on to provide our cells with energy have
evolved to also be devastating killers.
Bacteria
will continue to evolve and occupy every niche that exists on Earth long after
we are gone. We depend on them, and we fear them. If we dare to change the
environments in which they exist you can be certain they will win the first
assault before we can fight back.
References
[i] L. Kappen, “Field measurements of carbon dioxide exchange of the Antarctic lichen Usnea sphacekta in the frozen state”, Antarctic Science (1), 1989.
[ii] Toni Gabaldon and Martijn A. Huynen, “Reconstruction of the Proto-Mitochondrial Metabolism”, Science 301 (2003)
[iii] Jeremy K Nicholson, Elaine Holmes, John C Lindon & Ian D Wilson, “The challenges of modeling mammalian biocomplexity”, Nature Biotechnology (22), 2004, (quoted in http://www.wired.com/medtech/health/news/2004/10/65252 (accessed 10 December, 2007))
[iv] Ibid.
[v] When dealing with many smaller life forms, pluralisation can be confusing. Bacteria is the plural of bacterium, whereas you can use viruses or virii as the plural for virus.
[vi] R.G. Eagon, “Pseudomonas natriegens, a marine bacterium with a generation time of less than 10 minutes.”, J. Bacteriology (83), 1962.
[vii] National Institute of Standards and Technology, “Cornell Discusses His Recovery from Necrotizing Fasciitis with Reporters”, http://www.nist.gov/public_affairs/newsfromnist_Cornell_mediaevent.htm (accessed 13 December, 2007)
[viii] http://www.ni.unimelb.edu.au/docs/forum/5-Carapetis.pdf (accessed 13 December, 2007) which takes its figures from Jonathan R Carapetis, Andrew C Steer, E Kim Mulholland and Martin Weber, “The global burden of group A streptococcal diseases”, Lancet Infect Dis (5), 2005.
[ix] WHO Statistical Information System, http://www.who.int/research/en/ (accessed 14 December, 2007)
[x] “Trialling a new vaccine for tuberculosis”, Wellcome Trust, http://www.wellcome.ac.uk/News/News-archive/Browse-by-date/2001/Features/WTX024018.htm (accessed 14 December, 2007).
[xi] Zink AR, Sola C, Reischl U, Grabner W, Rastogi N, Wolf H, Nerlich AG, “Characterization of Mycobacterium tuberculosis complex DNAs from Egyptian mummies by spoligotyping.”, J Clin Microbiol. (41), 2003.
[xii] Richard Fortey, “Life: An Unauthorised Biography”, HarperCollins, 1997.
[xiii] Martin Wiselka, personal communication, 7 November 2007.
[xiv] D. A. Ratkowsky, Jone Olley, T. A. McMeekin and A. Ball, “Relationship Between Temperature and Growth Rate of Bacterial Cultures”, J. Bacteriology (149), 1982.
[xv] Paul S. Mead et al, “Food-Related Illness and Death in the United States”, Centers for Disease Control, http://www.cdc.gov/ncidod/eid/vol5no5/mead.htm (accessed 18 December, 2007)
[xvi] World Health Organization, “Diarrhoeal Diseases: Typhoid Fever”, http://www.who.int/vaccine_research/diseases/diarrhoeal/en/index7.html (accessed 18 December, 2007)
[xvii] Philippe Roumagnac et al, “Evolutionary History of Salmonella Typhi”, Science (24), 2006.
[xviii] Buddha Basnyat, Ashish P. Maskey, Mark D. Zimmerman and David R. Murdoch, “Enteric (Typhoid) Fever in Travelers”, CID (41), 2005
[xix] Spike Milligan (edited by Jack Hobbs), “Mussolini: His Part In My Downfall”, Penguin Books, 1978.
[xx] I won’t pretend to have remembered this word for word, I have The Simpsons Archive (http://www.snpp.com/episodes/7F19.html) to thank for the extract.
[xxi] Centers for Disease Control, “Lyme Disease --- United States, 2001—2002”, http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5317a4.htm and “Lyme Disease --- United States, 2003—2005”, http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5623a1.htm (accessed 20 December, 2007)
[xxii] Kathleen LoGiudice et al, “The ecology of infectious disease: Effects of host diversity and community composition on Lyme disease risk”, PNAS (100), 2003.
[xxiii] World Health Organization, Weekly Epidemiological Record (79), 2004, http://www.who.int/wer/2004/en/wer7933.pdf (accessed 20 December, 2007)
[xxiv] Keith Farnish, “What If…We All Became Vegan?”, The Earth Blog, http://earth-blog.bravejournal.com/entry/17001 (accessed 20 December, 2007)
[xxv] T.E. Amerault and T.O. Roby, “Card test an accurate and simple procedure for detecting anaplasmosis”, World Animal Review, 1981, http://www.fao.org/DOCREP/004/X6538E/X6538E04.htm (accessed 13 June, 2008).
[xxvi] Secretariat of the Pacific Community, “Cattle Tick”, http://www.spc.int/rahs/Manual/BOVINE/CATTLE%20TICKE.HTM (accessed 20 December, 2007)
[xxvii] For example, all leopards are of the same genus as each other, as are all honey bees.
[xxviii] Chris J. D. Zarafonetis, “The Typhus Fevers” in “Internal Medicine In World War II”, http://history.amedd.army.mil/booksdocs/wwii/infectiousdisvolii/chapter7.htm (accessed 20 December, 2007).
[xxix] David W. Tschanz, “Typhus Fever On The Eastern Front In World War I”, http://entomology.montana.edu/historybug/WWI/TEF.htm (accessed 20 December, 2007)
[xxx] Michael W. Gray, “Rickettsia, typhus and the mitochondrial connection”, Nature (396), 1998.