|A malaria causing plasmodium|
Tuesday, 28 May 2013
Wolbachia vs. malaria – we may be the real winners
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.
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.