• Hugo Creeth

Malaria: Is it Spreading?

Malaria Overview

Malaria is a dangerous and killer parasitic disease that is carried by infected mosquitoes and transmitted to/between people. Its prevalence is widespread and the risk of contracting the disease affects approximately half of the worlds 7 billion population size. It caused between 473,000 and 789,000 deaths in 2012 with around 207 million worldwide cases in that same period. The majority of these cases occur in sub-Saharan Africa, where a child dies every minute from the disease.

Mosquitos (specifically the Anopheles type) are the main vector of the disease, which is caused by Plasmodiumparasites. These parasites are divided into four main disease causing species. Plasmodium falciparum and Plasmodium vivax are the two most common species with the latter being the most deadly.

There are numerous factors that influence the rates and overall intensity of transmission of malaria, such as the vector, the human host and the environment. All Anopheles mosquitoes breed in water and bite at night. These variables result in seasonal variations in malarial transmission and malaria hot spots developing. Despite global mortality rates falling by 42% since 2000, malaria is still a major concern for the World Health Organisation (WHO)and its eradication is still a major priority in the area of disease prevention research.

Latest Breakthrough

A paper published in the journal Proceedings of the National Academy of Sciences focuses on the latest findings from a collaboration between researchers at Imperial College London, Harvard School of Public Health and the University of Perugia.

Female Anopheles mosquitoes only mate once in there life time, but reproduce many times. They do this by storing the sperm from this lone reproductive event in an organ known as the spermatheca. Ingeniously the action of sex in this species triggers several mechanisms that preserve the functionality and health of the sperm ensuring their viability for multiple future fertilisations.

Until now these mechanisms have not been known. Now Dr Robert Shaw and his team have managed to isolate and show the function of a specific enzyme, called heme peroxidase (HPX15) in this fete of preservation. HPX15 is activated during sex by the release of a hormone (20E) from the male mosquito into the female. This hormone initiates the activation of HPX15 expression in the female conveying protection of the stored sperm from dangerous free radicals (or Reactive Oxygen Species - ROS). These ROS are what are thought to cause the reduction in fertility seen after a blood feed, which is when the female mosquitoes lay their eggs. This is because the free radicals are most abundant after such events. Interestingly this steroid hormone is released in much smaller quantities after each feed by the female herself, which may also help promote HPX15 expression/activation and soak up the ROS.

In the laboratory the processes involved with finding this secret sperm saving enzyme, came from injecting female mosquitoes with an inhibitor that directly reduced HPX15 levels. This had the effect of increasing infertility from 3% too 20%. Something that although not much more than a fifth, is thought to almost certainly have a larger impact on wild mosquitoes, due to increased environmental load.

The way that HPX15 strictly works on a molecular and physiological level is still unknown. Understanding this would allow for a more targeted approach to controlling its expression and potentially limiting the fertility of the mosquitoes. The authors have speculated that it could work directly through its release into the spermatheca itself, or indirectly on the physiology of the sperm cells. Peroxidases have long been associated with the health of sperm cells. In mammals GPX5 (glutathione peroxidase) is released into the sperm storage sites of males attaching to sperm cell membranes ands helping prevent DNA damage. Therefore without the peroxidases it is hypothesised that DNA damage and other damage to the sperm themselves may cause downstream effects on embryo development.

What this means...

Malaria is a complicated disease by its very nature. Parasites have complex multi-stage life cycles meaning combatting them with a single line of attack is unlikely to be effective and sustainable. What this research offers is a potential untapped method of attack against one of the worlds deadliest diseases. Reducing or indeed potentially eliminating the fertility of the vector of malaria would only be a good thing for limiting its transmission rates and thus controlling the disease. Further work is needed into the exact role HPX15 and 20E have in the fertility of mosquitoes, but it is undoubtably an interesting angle of approach to a problem that needs solving. The previous finding that reduced HPX15 activity also helps lower plasmodium infection rates within a local population of mosquitoes highlights the future usage of HPX15 as a target for vector control strategies.

Mating activates the heme peroxidase HPX15 in the sperm storage organ to ensure fertility in Anopheles gambiae W. R. Shaw and E. Teodori and S. N. Mitchell and F. Baldini and P. Gabrieli and D. W. Rogers and F. Catteruccia Proc Natl Acad Sci U S A   (2014)

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