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Halting the World’s Most Lethal Parasite
Kumar Neelotpal Shukla 49001864
Nijansh Verma 49001865
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INTRODUCTION
The disease, its history and the need for a vaccine
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Malaria is a mosquito-borne infectious disease of humans and other animals caused by parasitic protozoans of the genus Plasmodium.
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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.
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Malaria causes symptoms that typically include fever and headache, which in severe cases can progress to coma or death.
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Current Status Worldwide
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The History
2700 BC
476 AD
China | References to the unique periodic
fevers of malaria found.
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".
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History
1820 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".
1880
1894 Calcutta & London | Sir Ronald Ross proved the complete life-cycle of the malaria parasite in mosquitoes.
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History
1917 Austria| Plasmodium vivax was used for malariotherapy.
Use of DDT to combat Malaria 1939
1940 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.
1950
1967 The first promising studies demonstrating the potential for a malaria vaccine were performed.
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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
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MECHANISMS
Parasite Life Cycle, Infection and potential Resistance mechanisms
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Strategy 1 Blocking Transmission
Antibodies mask enzyme
and gametocytes
die
Antibodies ingested by mosquitoes along with
gametocytes
Human injected with
Aminopeptidase; make
antibodies
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The “Immunological Bed Net”
The antibodies mask the amino peptidase enzyme in the mosquitoes’ guts, hanging around and preventing the parasite from targeting it.
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Strategy 2 Culturing Weak Parasites
Vaccine injected into humans to
trigger immune response
Compromised parasites are
extracted
Grow genetically modified
parasites in mosquitoes
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Live Labs – Mosquitoes
Mosquitoes carry genetically
damaged parasites
Parasites enter human
bloodstream and enter liver
Unable to mature,
parasites get stuck and die
The concept
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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.
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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.
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Strategy 3 Boosting a Traditional Vaccine
Vaccine injected into
child, booster shot after 1.5
years
Adjuvant added to enhance immune response
Proteins isolated from
healthy sporozite
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CASE STUDY
Study about the RTS, S vaccine by GlaxoSmithKline
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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.
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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.
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Effectiveness
As of October 2013, RTS,S, is said to have reduced the amount of cases to almost
25% among infants
50% among young children
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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.
Hurdles to Introduction
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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.
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Current Status
GlaxoSmithKline has said that it will set the price very low, with a small profit of 5%.
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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.
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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.
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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/interactive/malaria.html
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THANK YOU
Questions?
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DISCUSSION
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TOPIC – 1
• Of the three strategies mentioned, which one is the best? Also, any ideas about developing a vaccine based on your selection.
Antibodies mask enzyme
and gametocytes
die
Antibodies ingested by mosquitoes along with
gametocytes
Human injected with
Aminopeptidase; make
antibodies
Vaccine injected into humans to
trigger immune response
Compromised parasites
are extracted
Grow genetically modified
parasites in mosquitoes
Vaccine injected into
child, booster shot after 1.5
years
Adjuvant added to enhance immune response
Proteins isolated from
healthy sporozite
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TOPIC – 2
• Is vaccination the ultimate cure? Or should we look towards preventive medication and techniques?