Advancements In Our Battle Against Malaria

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Malaria is a disease spread by mosquitoes and causes around 500,000 deaths each year. Although preventative measures can be taken there is no licensed vaccine on the market, but this is believed to be one of the only factors which can eradicate this disease. To this day, researchers continue to make advancements in this search which contribute to an increased chance of combatting the bloodthirsty vectors.

The parasite was discovered in 1897 by Laveran, a French army doctor but, even after 123 years, humans still do not possess a definite vaccine. The main reasoning behinds this correspond with the unknown inner-workings of the human immune system, and malaria’s advanced ability to evade its response; this is particularly complex for the plasmodium falciparum parasite which causes the most severe form of malaria. There are also economic factors to consider and the large scale investments required to take on such a long-term and dynamic project. [3]

In 1972 Chinese researcher Tu Youyou discovered a compound, Artemisinin, proven to be efficient in combatting malaria, which she has since received the 2015 Nobel prize for. To identify the molecules Artemisinin binds with, an alkyne-tagged artemisinin analog was produced with biotin attached, and this was incubated with a live parasite. The results presented over 100 proteins capable of binding with the drug, later discovered to inhibit biochemical processes in the parasite, causing its death. [1]

A diagram presenting the mechanism of Artemisinin [1]

Sporogonic cycle: the sexual phase when malaria replicates in the mosquito

Ivermectin, discovered by Satoshi Ōmura and William C. Campbell, targets the sporogonic phase in mosquitoes, proving it to be effective in malaria control. This occurs as the drug binds to gated chloride channels in muscle and nerve cells of invertebrates, whilst increasing the cell’s permeability to the same ion. This alters the chemical gradient which in turn affects the neurosynpatic transmissions which control motor movement and muscular contraction; this results in flaccid paralysis and death. The same effect does not occur in humans as we do not possess the specific channels ivermectin binds to, meaning the drug does not pass our blood-brain barrier into our CNS, but is instead distributed to adipose tissues. [4][7]

There have been over 40 clinical trials involving malarial vaccines, yet the only drug to have continued to phase III was ‘RTS,S’; developed by GlaxoSmithKline (GSK) in 1987. During phase I and II GSK collaborated with seven African countries to enrol a small number of citizens into their trials, as this continent has the most frequent malaria epidemics so is an evident target for treatment. The promising results presented decreased severe cases in one-third of five to seventeen-month-olds after three doses of the vaccine and one booster dose. It appeared that the vaccine was more effective on this age category compared to young infants, but some adverse effects such as meningitis and cerebral malaria were detected. [2]

In simple terms, RTS,S works by producing antibodies, specific to the circumsporozoite protein (CSP) antigens present on the protist. These antibodies fix and activate complement; this antibody-complement activation can kill mosquitoes and prevent further infection in local individuals. [5]

Further trials began in 2018 in Ghana, Kenya and Malawi involving hundreds and thousands of infants receiving doses of the vaccine annually, and has since been producing promising results. However, these results only consider specific age groups and only have around a 50% success so, although optimistic, the outlook could be improved.

A recent scientific breakthrough discovered the molecules behind mosquitoes’ attraction to blood by genetically modifying the vectors and observing which neurons fluoresce when consuming different compounds designed to mimic blood; this concoction consisted of ATP, sodium chloride, sodium bicarbonate and glucose. One set of neurons was activated by both the real and artificial blood, indicating that the mosquito viewed both similarly. This advancement can lead to drug inventions which mask the smell of blood, preventing them from detecting humans in the first place, and ultimately eradicating both infection and transmission[6]

Overall, there are many treatments which have some impact on the symptoms or prevalence of malaria in the human population. However, most solutions are only useful post-infection, which does not answer the question of how to rid of the parasite or prevent any infection at all. With enhanced technology and discoveries of microbial techniques and new molecules, these steps in the right direction are capable of concluding with an effective vaccine.

References

  1. Celia Henry Arnaud, ‘Well-Known Malaria Drug Artemisinin Works By Attacking Multiple Parasite Proteins’, C & EN, 4 Jan, 2016
  2. Kashyap Vyas, ‘Advancements in Malaria Treatment in 2019’, Interesting Engineering, 13 July, 2019
  3. ‘How to Reduce Malaria’s Impact’, CDC, 25 Jan, 2019
  4. Dziedzom Komi de Souza, Irene Larbi, Daniel A Boakye, and Joseph Okebe, ‘Ivermectin treatment in humans for reducing malaria transmission’, NCBI, 4 Sep, 2018
  5. James Beeson, ‘How does the RTS,S malaria vaccine work?’, Nature Microbiology Community, 18 Mar, 2019
  6. Tess de La Mare, ‘Scientists discover why mosquitoes are so attracted to human blood’, Independent, 13 Oct, 2020
  7. Alex Matthews-King, Independent, ‘Drug which makes human blood ‘lethal’ to mosquitoes can reduce malaria spread, study shows’, 14 Mar, 2019

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