In early
December of 2013 while scanning my Twitter feed I spotted a very curious
retweet from Helen Branswell (@HelenBranswell), a medical reporter for the Canadian
Press who is a great source of updates on the spread of the MERS virus in the
Middle East. What caught my eye was that Helen was not posting about MERS or
Influenza (another topic she frequently tweets about) but she was retweeting a
story about an African fever virus called Chikungunya and it wasn’t in Africa, it was in St. Martin in the Caribbean.
My first
thought was this was an interesting curiosity, a few folks had traveled to
Africa on holiday, been bitten by the mosquitos that were infected with the
virus and traveled back home incubating the virus. This sort of little
accidental infection limited to a few individuals occurs
routinely in our age
of rapid travel so it is not uncommon these exotic sounding diseases get a
short excursion from their natural habitat, but the conditions in the other
parts of the world usually prevent them from becoming established. So although the
report of 10 people infected with Chikungunya on a Caribbean Island was a bit
unusual, at first I thought this would just be another short story for public
health history archives.
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| Sometimes we bring back a little more than we bargain for |
It's Complicated!
But ten
people is an interesting cluster to me and just a little quick reading of some
of the recent research on this virus had me reconsidering my assumption. I hadn’t
thought of Chikungunya since graduate school virology class
in the 80s so I was surprised to learn a lot of things have changed in the
story of how this disease is transmitted since then. Airline industry experts
are constantly telling us, “it is never just one thing that brings down an
airplane, it is a series of problems or malfunctions that result in a crash”.
This once obscure African fever, Chikungunya has a similarly framed story. It
wasn’t just any one particular event that led it out of Africa, and clearly it
is now well established outside of Africa. Some very fascinating evolutionary
events involving a virus and the mosquitos that transmit it intersected with
changing human behaviors and practices. As a result the course of this virus
has altered remarkably and Chikungunya is on the move.
Really, The Name Says It All
From the Makonde
language Chikungunya translates into English as, “that
which bends up” and in Swahili the word means “the illness of the bended walker”.
The name refers to the painful arthritic condition that is associated with a disease
that typically persists for weeks, can last for months and on occasion even
years following an acute bout with this virus. There is no vaccination to
prevent it and there are no drugs to specifically treat it, the symptoms
including high fever and extreme joint pain are managed until the illness runs
its course. It is rarely fatal, but it often makes the aching feverish patient
wish they would die, at least in the short-term.
The
Chikungunya Virus (CHIKV) was first detected in 1952 in the African Makonde
Plateau, an area on the border of Mozambique and Tanzania. It is one of those
“fever” viruses that we tend to associate with central Africa and I had assumed
it was safely confined to central Africa, but CHIKV has been on the march and the
story of this journey is pretty amazing. For most of its history CHIKV was
confined to the forest in the central portion of east Africa. It’s a virus and
just like all viruses it seems to have one only one purpose. It wants to make
more copies of itself. That is how a virus species survives. But unlike most
other forms of life that we classify as living, viruses are not capable of
making more viruses on their own, they must have help.
Viruses Really Can't Be Left On Their Own
Viruses require a living
organism to act as their host. All plants and animals and even many bacteria
and fungi are known to be susceptible to viruses. Not just any animal or plant
will do for a particular species of virus, viruses for the most part are very
picky about their specific host. A virus is considered to be an obligate
intracellular parasite meaning it is dependent on that specific host that it is
compatible with in order to survive and produce more copies of itself.
Although
viruses require a host, most potential hosts usually don’t want to house a
virus. For the most part viruses make lousy guests. When a virus enters a host,
it finds the cells that it needs to make more copies of itself and if it can
get into those cells usually the problems for the host begin pretty quickly and
outweigh any advantages of having a viral guest. When the virus enters a
suitable host cell it makes the machinery in the cell stop performing whatever
function it is supposed to be conducting for the host and it reprograms the
cell to start making more copies of the virus. Essentially a hijacking has
occurred and the essential functions that cell had been providing for the host
are discontinued. That infected cell has been converted into a little viral
factory that pumps out multiple copies of viruses that in turn infect more
cells and the process keeps spreading.
This will
only keep happening for a defined period of time. Either the host’s immune
system kicks in and starts fighting back and will destroy the virus or the
virus will keep working the enslaved cells of the host forcing them to make
viruses until they are exhausted and destroyed. If enough damage is done the
host finally dies. Either of these outcomes is no good for the virus if is
remains trapped inside the host, so the virus must have an escape plan. Once
infected, a host is only suitable for a limited period of time so timing is
very important on the virus’s part. If the species is to survive it must get
out of this host and into another one. That’s the role of the mosquito in this “vector
transmission” (or spread if you prefer) of CHIKV. Although CHIKV doesn’t usually
kill its host, the virus must get out of that host and into another host before
the immune system gets wise to it and destroys it. The virus gets helicoptered
(actually mosquitoed) out of one host and into another host to start virus
production all over again. This insures survival of the virus.
Chikungunya Forms A Partnership
So probably
thousands, maybe millions of years ago CHIKV and nature worked out a very
suitable cycle that created a complex but efficient arrangement between
nonhuman primates (apes), a specific species of mosquito called Aedes aegypti (A. aegypti) and CHIKV. These apes were once plentiful in the east
central African forest, the female mosquito needed the blood of the ape to
nourish the eggs that would become her offspring and the virus figured a way to
attach and survive in that particular mosquito species and when she fed on an ape
infected with CHIKV, the virus would slip into the mosquito with the blood meal
and would remain in the midgut of the mosquito. When the mosquito later fed on
an uninfected ape she deposited the virus while she fed and the virus soon
setup viral production in this new host ape. This cycle worked very efficiently
until humans entered the picture. Successful transmission of a virus requires a
little genetic level trickery the part of the virus that involves the proteins
on the virus surface. The first trick is that its proteins must be compatible
with the proteins in the mosquito so that the mosquito could actually tolerate
its presence. Otherwise the mosquito’s immune system would destroy the virus
when it realized it was “foreign to its body”. The viral proteins had to be
sufficiently compatible so that the mosquito wouldn’t consider it a threat. So
some sort of détente is achieved between the mosquito’s immune system and the
virus so that the virus doesn’t harm the mosquito. Then it had to perform some similar magic once
it got into the host. It had to trick the ape’s immune system into thinking it
wasn’t a problem so the proteins on the virus had to also be able to evade the
ape’s immune protections in order to penetrate a suitable cell. Once inside the
cell, the hijacking begins. The virus knows it only has a limited window of
opportunity to do its work. The host immune system is going to eventually
figure out there is an intruder and when the war to rid the ape of the virus
starts it will be severe. There is no time to waste, the cell is forced to
begin production and the pace is fast. The virus has to prepare to get into
that escape mosquito as soon as it presents itself.
Humans Enter the Equation
The
intrusions of humans into this non-human dominated forest began to interrupt
this long established cycle. The mosquitos began to try to feed on these new
primates, the humans. After all, they still required a blood source for their
offspring so a mutation in proteins of the mosquitos meant strains of A. aegypti mosquitos that lived off
human blood began circulating in the forest alongside strains of the species
that fed off traditional non-human primates. At first when those mosquitos
dumped the CHIKV virus into humans the virus was destroyed because the human
immune systems recognized those surface proteins as “foreign”. As urban
settlements began to establish themselves in the interior, the population of
non-human primates began to dwindle so more and more frequently humans were
being bitten by CHIKV infected mosquitos. Viruses are always making mutations,
most don’t survive, but eventually mutations that resulted in proteins that
fooled the human immune system were created. It was as if nature was doing
market research and preparing for a consumer shift. The forest population switch
from non-primate to humans in the forest was a challenge for CHIKV. But nature
is resourceful. The CHIKV virus also began to evolve itself. The new mutations
that infected humans were becoming established and circulated along with the
strains that still fed on apes as long as they were available. By the mid part
of the 20th century there were multiple small outbreaks where the
CHIKV was transmitted to humans through the bites of the mosquitos.
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| Transmission cycle for Chikungunya between humans |
The protein structures on the surface of the
virus altered and the strains that contained proteins that allowed for the
attachment of human cells began to thrive. This meant that those infrequent
human outbreaks could become more frequent since the mosquitos began to
circulate more virus capable of attacking humans more frequently. Still the CHIKV
mosquito to human transmission was confined to this area of the African
continent because the only mosquito that was capable of transmitting CHIKV was
the A. aegypti. A new successful
balance had been obtained, the virus had found a means to survive and thrive in
its cozy little corner of the world. The infected mosquitos and the infected
hosts (both apes and human) were isolated enough that the disease would run its
course in this new cycle without having a real opportunity to travel. Humans
had gone to great lengths to keep the A.
aegypti mosquito isolated.
The Mosquito With The Sordid Past
By the
discovery of the CHIKV in the 1950s, A.
aegypti was well
known to be a vector for some pretty nasty viruses besides CHIKV. The Yellow Fever Commission led by Walter Reed had identified A. aegypti as the vector for Yellow
Fever at the beginning of the 20th century before it had even been
proven that Yellow Fever was caused by a virus and since that time the A. aegypti mosquito had been revealed to
be the vector for Dengue Fever, Malaria and was suspected to transmit a number
of other diseases. For much of the first half of the 20th century
impressive public health campaigns were carried out to shrink the habitats of
the A. aegypti mosquitos. The species
had been widely distributed around the world but sanitation campaigns to reduce
their numbers in urban areas were very effective along with powerful
pesticides. The population was well controlled and as a result, the A. aegypti mosquitos began to disappear
from much of the urban world and along with it those great epidemics of Yellow
Fever disappeared from North American and European cities. While small pockets
of A. aegypti mosquitos remained in
swamps and marshes in some of those areas, those populations were not infected
with the Yellow Fever Virus. Yellow Fever was now primarily confined back into
the sparsely inhabited forests of Africa and South America where it once again primarily
circulated between mosquitos and non-human primates, only occasionally making
its way into the urban areas of those regions. When A. aegypti was contained so were the other diseases it transmitted such
as Malaria and CHIKV.
But nature is
determined to have its way. Viruses continue to evolve and these resulting mutations
will occasionally persist. The proteins that make up a virus determine its
behavior. When those proteins alter, so do the behaviors. It was an alteration
in those proteins that first allowed the CHIKV to infect humans in addition to
the original non-human primates. Humans played a key role in driving another
protein change in this balance when their behaviors shifted the mosquito
populations in this area of the world. When the A. aegypti population began to shrink, nature once again kicked the
CHIKV into survival mode, and the search for a new mosquito host began. What
was actually happening was at some point the humans and the apes were being
bitten more and more frequently by the growing populations of the new species
of mosquitos and less and less often by the shrinking numbers of the displaced A. aegypti. Nature is resourceful, so it
was inevitable mutations that would survive in the new species of mosquito
would arise as they begin to take over the territory.
When You Block Her Path, Nature Finds A Way: A New Vector Emerges
While we were
busy ridding the world of A. aegypti and
eliminating all those nasty epidemics associated with it, we completely ignored
its “little cousin” Aedes Albopictus. It turns out this was an epic
oversight on our part. A. aegypti was
indeed a nuisance to us, but it was usually because we invaded the wet and
boggy areas that it had populated first and we then intruded. It didn’t want to
live with us, we took its territory. However it turns out A. Albopictus enjoys our company, actually thrives in our midst. It
takes advantage of the opportunities that we provide for it in our environment.
Just about any little moist area that we create in our urban world, it will
use. It is particularly bothersome to us because unlike A. aegypti who prefers to bite from dusk until dawn, A. Albopictus feeds on us all day long.
It earned itself a common nickname that is very descriptive of its appearance
and some say its attitude, the Asian Tiger Mosquito. Tiger because of the
stripes it sports and some would say its aggressive biting behavior, but Asian
because it was found exclusively in Southeast Asia until it found how desirable
it was to live and travel with us just about wherever we go. Once again, it was
not a single event, but a combination of factors that permitted the spread of A. Albopictus from Asia.
Our Short Collective Memory Sets Us Up for Disaster
As it happens
so often, once we stopped having those epidemics of Yellow Fever and Malaria of
biblical proportions the traumas of these outbreaks left our collective
memories and we began to tire of spending money on sanitation and public health
programs. If we don’t see a problem, it really just doesn’t exist. We largely
stopped our public mosquito eradication and control programs as a way to “save
money”. Populations of A. aegypti began
to recover. Most of them were absent of the viruses that causes the diseases
and the parasites that caused Malaria, but the vector (mosquito) populations
did rebound.
Meanwhile, A. Albopictus got its chance to spread
thanks to our consumption and wasteful lifestyle as humans and our enterprising
ways to efficiently ship both our consumer goods and our waste products. By the
1960s A. Albopictus had been detected
in India and in the Pacific Ocean region. This initial venture out of
Southeast Asia was most likely aboard ships loaded with goods for trading. In
1979 it was discovered to have migrated to Albania among goods shipped from
Japan. It then found its way to the United States at the Port of Houston in
1985 among a shipment of used tires from Asia. It was not confined there, it
spread throughout most of the Southeastern US and even as far up the eastern
seaboard as the coast of Maine. It was soon discovered that the enormous quantity
of used tires being shipped around the world was playing a very efficient role
in transporting A. Albopictus to new
areas where it had never been seen. In 1991 it was exported from the U.S with
used tires shipped from Georgia to Italy and it spread from there throughout
the Mediterranean and Europe, even into the Swiss Alps. This
When the protein
changes occurred that
allowed CHIKV to begin using A.
Albopictus as a vector between humans, the CHIKV had at last found its ride
out of the forest and its means to transition itself not just into a world
traveler, but into a global resident. As different strains of A. Albopictus began to be established in
different parts of the world, we began to realize this might be an efficient
transportation network for many previously isolated diseases.
As the
populations of A. Albopictus began to
thrive in Africa, studies revealed that African
strains of the species were now very competent vectors for many viruses that
had previously been exclusively seen in the native populations of species such
as A. aegypti. These included Yellow
Fever, Dengue Fever, Rift Valley Fever, West Nile Virus and CHIKV. Researchers
in Nigeria also noted that A. Albopictus
was becoming well established globally and was rapidly displacing A. aegypti as the dominant mosquito in
many areas. Its more aggressive nature and hardiness could mean that the risk
of these diseases spreading farther and faster was a real possibility.
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| Old tires may no longer transport us but they suit mosquitos well |
The viruses were changing and their vectors were changing. Our
moving into their habitats had altered their habits and our introducing our inventions
and waste products had altered their behaviors. It’s ironic that when tires
cease to function as transportation for us, they have become an efficient
vehicle for transporting mosquitos.
It’s never a
quick or simple story
Not all the strains of the viruses have evolved in the
same manner. Neither have all the mosquitos. Researchers have concluded that
some strains of A. Albopictus found
in North American have evolved into becoming competent vectors capable of
transmitting Yellow Fever and Dengue Fever under certain environmental
conditions. So now apparently at least some of them have evolved to be able to
effectively transmit CHIKV in the Caribbean area of St. Martin. The case toll
has climbed. The outbreak of ten initial cases reported in St. Martin in
December of 2013 has now escalated into over 700 cases of CHIKV being reported
in eight different Caribbean area islands and countries as of late January 2014 and 498 new cases were reported in one week alone in
January.
The virus is now known to be
set up and circulating in the A.
Albopictus mosquito population in the Caribbean region and the mosquitos
are transmitting it as they bite infected people and then next feed on
uninfected and susceptible people. This means for us in Florida that CHIKV is
only a couple of days away by ship and a few hours away by air from us and our
huge population of A. Albopictus
mosquitos. If an infected person disembarks here and is bitten by our local A. Albopictus it is indeed possible for
them to start the cycle of transmission here if the local population of mosquitos
has evolved to host the virus. But is this likely to occur? Many experts think
it can, but studies are still underway to determine if the various strains of A. Albopictus here in the US can
transmit CHIKV, and if they can will environmental conditions be favorable for
this to happen.
Science To The Rescue
I was curious
to learn more about these studies of the
A. Albopictus and transmission risks.
As a kid I read and marveled at those stories about the experiments conducted
by dashing public health heroes such as Carlos Finlay, Jesse Lazear, Walter
Reed and my personal hometown favorite son from Mobile, William Gorgas as well as many others who unraveled
secrets about disease transmission. There were stories of scientists who
frequently became ill with the diseases they studied, more than a few lost
their lives. Today scientists realize the story of transmission is even more
complicated than envisioned by those early researchers. There are a number of
factors that are involved before a virus can establish itself in a new geographic
region. In the case of CHIKV, these include more than just the presence of the
appropriate mosquito acting as its vector. The environment and the climate both
play roles in establishing the vector as well as the virus.
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| Transmitting the virus to the mosquito the slow way |
Research
techniques and tools have certainly advanced since those early 20th
century pioneers did their extraordinary groundbreaking work, but one study I
reviewed described a technique that I had never even imagined and it caught my
interest straight away. That technique is referred to as the mosquito enema. Obviously
studying the various strains of mosquitos as well as the various strains of
virus is painstaking and complicated work with many unique challenges, but
learning that scientists were actually capable of giving a mosquito an enema
was as fascinating to me as the reason they were doing it.
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| Today's rapid technique for infecting a mosquito |
So, why give
the mosquito an enema? It seems that the method in which
the mosquitos being infected with CHIKV can influence the accuracy of
transmission predictions. We’ve come a long way from the days of feeding
mosquitos a virus induced blood meal where volunteers stick their arms into
mosquito filled cages. That was an effective but slow research method. In
addition to the oral feeding of the mosquito with virus infected blood,
scientists learned that work could proceed more efficiently by administering
the CHIKV virus by either intrathoracic injection or by administering the virus
via an enema. It seems that the enema route offers the advantage of getting the
virus into the midgut faster than the oral route and without the introduction
of a wound caused by the injection. Some rather intricate methods are necessary
to get a better understanding of which mosquitos can transmit which viruses and
where. It seems in order to obtain meaningful data on transmission, some very
precise laboratory techniques as well as unique skills are required to conduct
this research.
Where in the World Is Chikungunya Headed Next?
So where are
we today? Well in the case of Florida, many researchers have concluded we
probably have cause for concern. Already in our extreme southern counties the A. aegypti population has rebounded and
they are transmitting Dengue Fever. The cases of locally acquired human
transmission of Dengue have been rising for several years. But A. aegypti is the dominant mosquito in only
specific parts of a few south Florida counties. All of the other counties in
Florida are dominated by A. Albopictus. It seems our little Asian Tiger friend
is just about everywhere in our state.
In
2008, a team led by Michael Reiskind from LSU published their findings after
studying various strains of Aedes mosquitos in the US and their conclusions
were that the populations of both A. aegypti and A. Albopictus in Florida
are capable of transmitting CHIKV. Other studies have demonstrated the climate
in south Florida may increase the risks for CHIKV establishing itself here rather
than other areas of the US where the virus may also gain a point of entry.
 |
| The red shaded areas indicate U.S. geography there A. Albopictus is established. |
In other areas of the US, the large swings in seasonal
temperatures make it unlikely the virus will be able to be transmitted year
round. However the smaller temperature swings between seasons in south Florida increases
the likelihood that the virus could be successfully vectored by the mosquitos
there. This increases the possibility of year round transmission of CHIKV in
south Florida where there is so much human year round outdoor activity.
It’s not a
forgone conclusion that we will see CHIKV establish itself in south Florida,
but when we examine the journey of the virus and the mosquito, it doesn’t seem
such a far stretch any longer. Already there are calls for an increased
vigilance of our mosquito populations and the appropriation of funding to
increase eradication programs. In the Florida Keys
the use of genetically modified mosquitos to curve the population of A. aegypti that has been transmitting
Dengue is being studied but is meeting a lot of opposition from anti-GMO groups. No one doubts that CHIKV is on the
move again, it will be interesting to see if Florida is in fact a new
destination.
Recommended Sources For Additional Chikungunya Information:
Chikungunya Virus Net.com http://www.chikungunyavirusnet.com/
Centers for Diseases Control and Prevention (CDC.gov) http://www.cdc.gov/chikungunya/pdfs/CHIKV_VectorControl.pdf
European Centre for Disease Prevention and Control http://www.ecdc.europa.eu/en/Pages/home.aspx
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