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Halting the World's Most Lethal Parasite: Malaria

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About malaria and strategies to counter it.

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Halting the World's Most Lethal Parasite: Malaria

  1. 1. Halting the World’s Most Lethal Parasite Kumar Neelotpal Shukla 49001864 Nijansh Verma 49001865
  2. 2. The disease, its history and the need for a vaccine INTRODUCTION
  3. 3. Malaria is a mosquito-borne infectious disease of humans and other animals caused by parasitic protozoans of the genus Plasmodium.
  4. 4. Commonly, the disease is transmitted via a bite from an infected female Anopheles mosquito, which introduces the organisms from its saliva into a person's circulatory system.
  5. 5. Malaria causes symptoms that typically include fever and headache, which in severe cases can progress to coma or death.
  6. 6. Current Status Worldwide
  7. 7. 2700 BC China | References to the unique periodic fevers of malaria found. The History 476 AD Rome | Malaria may have contributed to the decline of the Roman Empire, and was so pervasive in Rome that it was known as the "Roman fever".
  8. 8. History 1820 1880 1894 France | Pierre Joseph Pelletier and Joseph Bienaimé Caventou isolated Quinine, the first effective antimalarial treatment. France | Charles Louis Alphonse Laveran observed parasites inside the red blood cells of infected people for the first time and proposed that malaria is caused by this organism". Calcutta & London | Sir Ronald Ross proved the complete life-cycle of the malaria parasite in mosquitoes.
  9. 9. History 1917 1939 1940 1950 1967 Austria| Plasmodium vivax was used for malariotherapy. Use of DDT to combat Malaria South Pacific | Malaria was the most important health hazard encountered by U.S. troops in the South Pacific during World War II. About 500,000 men were infected. Chloroquine replaced quinine as the treatment of both uncomplicated and severe malaria. The first promising studies demonstrating the potential for a malaria vaccine were performed.
  10. 10. The Need for Vaccine Age-standardised disability-adjusted life year (DALY) rates from Malaria by country (per 100,000 inhabitants). Malaria kills 2 million yearly -World Bank
  11. 11. Parasite Life Cycle, Infection and potential Resistance mechanisms MECHANISMS
  12. 12. Strategy 1 Blocking Transmission Human injected with Aminopeptida se; make antibodies Antibodies ingested by mosquitoes along with gametocytes Antibodies mask enzyme and gametocytes die
  13. 13. The “Immunological Bed Net” The antibodies mask the amino peptidase enzyme in the mosquitoes’ guts, hanging around and preventing the parasite from targeting it.
  14. 14. Strategy 2 Culturing Weak Parasites Grow genetically modified parasites in mosquitoes Compromised parasites are extracted Vaccine injected into humans to trigger immune response
  15. 15. Live Labs – Mosquitoes Mosquitoes carry genetically damaged parasites Parasites enter human bloodstream and enter liver The concept Unable to mature, parasites get stuck and die
  16. 16. DNA damaging methods Knock – Out • Knocks out only two genes, which normally help the parasite build a membrane around itself while it takes up residence in the liver cells. • Parasites without membranes promptly cause a liver cell to commit suicide rather than playing host to it.
  17. 17. DNA damaging methods Irradiation • Sanaria, Hoffman’s biotech company’s approach. • Radiation scrambles the genetic code in many more sites than two, it may be a safer, more complete way to ensure that the parasite cannot reproduce once it gets to the liver.
  18. 18. Strategy 3 Boosting a Traditional Vaccine Proteins isolated from healthy sporozite Adjuvant added to enhance immune response Vaccine injected into child, booster shot after 1.5 years
  19. 19. Study about the RTS, S vaccine by GlaxoSmithKline CASE STUDY
  20. 20. RTS, S – Mosquirix • RTS,S is the most recently developed recombinant vaccine. It consists of the P. falciparum circumsporozoite protein from the pre-erythrocytic stage. • It follows Strategy 3. • The CSP antigen causes the production of antibodies capable of preventing the invasion of hepatocytes and additionally elicits a cellular response enabling the destruction of infected hepatocytes.
  21. 21. Effectiveness • When tested in trials an emulsion of oil in water and the added adjuvants of monophosphoryl A and QS21 (SBAS2), the vaccine gave protective immunity to 7 out of 8 volunteers when challenged with P. falciparum.
  22. 22. Effectiveness As of October 2013, RTS,S, is said to have reduced the amount of cases to almost 50% 25% among young children among infants
  23. 23. Hurdles to Introduction Expense Developing RTS,S and getting it to market will end up costing hundreds of millions of dollars, so it could be too pricey for practical use in the developing world.
  24. 24. Hurdles to Introduction Inefficiency It is exceedingly unlikely that RTS,S will work as well as most vaccines for other diseases, which generally need to be at least 80 % effective before they are approved for wide use.
  25. 25. Current Status GlaxoSmithKline has said that it will set the price very low, with a small profit of 5%.
  26. 26. Current Status GlaxoSmithKline has said that it will set the price very low, with a small profit of 5%. it hopes that international consortia and organizations such as UNICEF and the Global Alliance for Vaccines and Immunization will buy the vaccine and distribute it to developing countries in Africa.
  27. 27. Current Status GlaxoSmithKline has said that it will set the price very low, with a small profit of 5%. it hopes that international consortia and organizations such as UNICEF and the Global Alliance for Vaccines and Immunization will buy the vaccine and distribute it to developing countries in Africa. GlaxoSmithKline is set to submit an application for a marketing license with the European Medicines Agency (EMA) in 2014.
  28. 28. References • Halting the World’s Most Lethal Parasite by Mary Carmichael. Scientific American, November 2010. • The Fever: How Malaria Has Ruled Humankind for 500,000 Years. Sonia Shah. Sarah Crichton Books, 2010 • http://en.wikipedia.org/wiki/Malaria • "Case studies: Potential malaria vaccine" (Press release). GlaxoSmithKline. August 21, 2009. • http://www.nature.com/nature/journal/v484/n7395_supp/int eractive/malaria.html
  29. 29. Questions? THANK YOU
  30. 30. DISCUSSION
  31. 31. TOPIC – 1 • Of the three strategies mentioned, which one is the best? Also, any ideas about developing a vaccine based on your selection. Human injected with Aminopeptida se; make antibodies Antibodies ingested by mosquitoes along with gametocytes Antibodies mask enzyme and gametocytes die Grow genetically modified parasites in mosquitoes Compromise d parasites are extracted Vaccine injected into humans to trigger immune response Proteins isolated from healthy sporozite Adjuvant added to enhance immune response Vaccine injected into child, booster shot after 1.5 years
  32. 32. TOPIC – 2 • Is vaccination the ultimate cure? Or should we look towards preventive medication and techniques?

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