It is estimated
that there are 220 million cases of malaria each year and a total of 3.3billion, half the world's population, at risk of the disease. The number at
risk is continuing to rise as climate change extends the regions in which the
vector for the malarial parasite, Anopheline mosquitoes, can live; making
malaria one of the most pressing issues of current infectious disease control.
Fortunately there are some preventative measures that can be taken to avoid
Anopheles mosquitoes as they are night biting - it's fairly easy to sleep under
a net in an area of risk. However, getting these nets to those in most need is
a different issue entirely. Fortunately, pathogens such as Plasmodium species
(the parasites that cause malaria) have a life cycle that involves stages in
two different organisms, opening a whole new avenue for preventative strategies.
If we can directly control the vector of disease, mosquitos, then this could
theoretically block human infection since the malarial parasite cannot pass
directly from human to human. Attempts have been made with the large-scale use
of insecticides or oil in the lakes where eggs are laid by mosquitoes, but
these approaches are costly and unsustainable. However, recent work has hinted
at a new method of control that may well be able to make an unprecedented
contribution to our fight against malaria, and moreover our fight against
another mosquito borne disease, dengue fever.
Similarly to
malaria, dengue fever is carried by mosquitoes, and over 2.5 billion people arethought to be at risk. There are two major, and important, differences between
the two diseases. Firstly, malaria is caused by a parasite while a virus is
responsible for dengue fever. Along with the different causative agents, the
two diseases are transmitted by two different species of mosquito, with malaria
being carried by Anopheles and dengue being carried by Aedes species. This has
important implications for control of disease. Aedes mosquitoes are day biting,
meaning that avoidance of the two species poses different challenges. While
sleeping under mosquito nets may work for malaria, this will have little impact
on control of dengue. However, the two diseases do have the important
commonality that they are both completely reliant on mosquitoes for spread, and
as such, cannot spread within a human population without their respective
vectors.
In 2011 results were published from a study looking at the possibility of directly controlling
the Aedes mosquito in an attempt to prevent human cases of dengue fever. A team
in Australia led by Scott O'Neill showed that it is possible to substantially
reduce the spread of dengue virus with the simple intervention of infecting
Aedes mosquitoes with bacteria and releasing them into the wild. The bacterial
infection responsible for this potentially remarkable breakthrough is from a
species known as Wolbachia, which naturally infects many arthropods.
Wolbachia have
evolved to spread between arthropods and invade the population. The main way
the bacteria are able to spread and become established is through an effect
known as cytoplasmic incompatibility (CI). If you imagine a cell like a
balloon filled with water, then cytoplasm is the water. Once inside the
mosquitoes, Wolbachia are capable of infecting germ line cells, these are the
sperm and eggs, and residing in the cytoplasm of these cells. Upon fertilization
of an egg by a sperm there is fusion between the two cells causing mixing of
the cytoplasm of each cell. If an infected male mates with a healthy female
then the fused cell is destroyed by the presence of incoming bacteria; meaning
there is no fertilization. However, if an infected male mates with an infected
female there is no issue, the sperm and egg, each with bacteria in their
cytoplasm, will fuse and there will be fertilization to give new offspring. Similarly,
if a healthy male mates with an infected female there will be successful
fertilization. This gives the bacteria a maternal inheritance pattern, as the
female always needs to be infected. The newly produced offspring will all carry
Wolbachia in their cells allowing invasion of the population by the bacteria.
In essence the Wolbachia bacteria have developed a way to kill off any
uninfected mosquitoes by making the adults sterile (for all intents and
purposes). Only infected mosquitoes are ever born once CI has taken true effect
within a population.
What makes
Wolbachia infection even more interesting (other than simply as an evolutionary
fascination) comes from the fact that infected Aedes mosquitoes are unable to
carry enough dengue virus to effectively transmit it to humans. It isn't fully
understood why yet, but it seems that this may be down to the mosquito mounting
an immune response against the bacteria that causes collateral damage against
the other microbe.
The effect of
Wolbachia on dengue transmission is beginning to look like a truly viable
option for control. However, dengue is just one of a whole host of mosquito
borne disease; sitting at the top of the list for those most desired to be
tackled is malaria. Much interest therefore stemmed from the dengue studies
into how this approach could be used for the control of malaria. However, for a
long time this proved elusive, that was until the last couple of weeks. A new study in China led by Zhiyong Xi has managed to find a species of Wolbachia
capable of invading an Anopheles mosquito species, and suppressing the level of
malaria within the mosquito.
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| A malaria causing plasmodium |
This is a major
breakthrough. Until this paper was published no Wolbachia species had been
found that was capable of becoming established within any Anopheles species.
What's more, the study showed that Plasmodium falciparum, which causes the most dangerous form of malaria,
was affected by the presence of Wolbachia. The next stage will be to release
infected mosquitoes into the wild and see if the bacteria can become
established outside of the laboratory setting. If these Wolbachia infected
mosquitoes can become established in the wild then we may well have a way to
significantly reduce the spread of a disease that so many people are at risk
from. Probably the best way to truly protect people from malaria will be to
develop a vaccine, but until we manage that we need other strategies to tackle
the infection. Our best strategy, at present, is the use of insecticides and
nets. However, getting nets to the poorest areas of the world, which are often
those most at risk, is not always an easy task. An easier goal may be to find a
way to block mosquitoes from carrying malaria, making their taking of a blood
meal essentially harmless. The discovery of a Wolbachia species able to
establish within Anopheles population brings us on giant step closer to
achieving this goal.
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