About malaria and strategies to counter it.

1. Halting the World’s Most
Lethal Parasite
Kumar Neelotpal Shukla 49001864
Nijansh Verma 49001865

2. The disease, its history and the need for a vaccine
INTRODUCTION

3. Malaria is a mosquito-borne infectious disease of
humans and other animals caused by parasitic
protozoans of the genus Plasmodium.

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. Malaria causes symptoms that typically include fever
and headache, which in severe cases can progress
to coma or death.

6. Current Status Worldwide

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. 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. 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. 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. Parasite Life Cycle, Infection and potential Resistance mechanisms
MECHANISMS

14. Strategy 1
Blocking Transmission
Human
injected with
Aminopeptida
se; make
antibodies
Antibodies
ingested by
mosquitoes
along with
gametocytes
Antibodies
mask enzyme
and
gametocytes
die

15. The “Immunological Bed Net”
The antibodies mask the amino peptidase
enzyme in the mosquitoes’ guts, hanging around
and preventing the parasite from targeting it.

16. Strategy 2
Culturing Weak Parasites
Grow
genetically
modified
parasites in
mosquitoes
Compromised
parasites are
extracted
Vaccine
injected into
humans to
trigger
immune
response

17. 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

18. 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.

19. 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.

20. 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

21. Study about the RTS, S vaccine by GlaxoSmithKline
CASE STUDY

22. 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.

23. 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.

24. 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

25. 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.

26. 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.

27. Current Status
GlaxoSmithKline has said that it
will set the price very low, with a
small profit of 5%.

28. 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.

29. 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.

30. 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

31. Questions?
THANK YOU

32. DISCUSSION

33. 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

34. TOPIC – 2
• Is vaccination the ultimate cure? Or should
we look towards preventive medication and
techniques?