Halting the World’s Most Lethal Parasite

Kumar Neelotpal Shukla 49001864

Nijansh Verma 49001865

INTRODUCTION

The disease, its history and the need for a vaccine

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

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.

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

Current Status Worldwide

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".

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.

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.

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

MECHANISMS

Parasite Life Cycle, Infection and potential Resistance mechanisms

Strategy 1 Blocking Transmission

Antibodies mask enzyme

and gametocytes

die

Antibodies ingested by mosquitoes along with

gametocytes

Human injected with

Aminopeptidase; make

antibodies

The “Immunological Bed Net”

The antibodies mask the amino peptidase enzyme in the mosquitoes’ guts, hanging around and preventing the parasite from targeting it.

Strategy 2 Culturing Weak Parasites

Vaccine injected into humans to

trigger immune response

Compromised parasites are

extracted

Grow genetically modified

parasites in mosquitoes

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

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.

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.

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

CASE STUDY

Study about the RTS, S vaccine by GlaxoSmithKline

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.

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.

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

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

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.

Current Status

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

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.

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.

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

THANK YOU

Questions?

DISCUSSION

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

TOPIC – 2

• Is vaccination the ultimate cure? Or should we look towards preventive medication and techniques?